Print Page | Close Window

Promising vaccines - Discussion

Printed From: TNBC Foundation
Category: TNBC Forums
Forum Name: TNBC Talk
Forum Description: A place to chat
URL: http://forum.tnbcfoundation.org/forum_posts.asp?TID=9549
Printed Date: Dec 08 2019 at 12:57am
Software Version: Web Wiz Forums 12.01 - http://www.webwizforums.com


Topic: Promising vaccines - Discussion
Posted By: christina1961
Subject: Promising vaccines - Discussion
Date Posted: Jan 28 2012 at 11:54am
Hi, Please let me know if I am posting this in the wrong spot but I was reading some articles this morning about cancer in general and found several very promising vaccines mentioned.
Here is a link to information about a viral vaccine, jx594 that looks interesting.  Apparently, when cancer cells throw off part of their regular cellular composition in order to promote fast growth, they also throw away what protects them against viruses.  This vaccine targets that weakness in the cancer cells to induce death in the cancer cell. 
 
http://www.jennerex.com/jx594.html - http://www.jennerex.com/jx594.html
 
I will also go back and see if I can post the original article because there are several such vaccines in progress.  This is just one that has some Phase I and Phase II trials open right now. I wanted to see what others in this group think about vaccines such as this one and the one being developed at Roswell Park in NY that currently is recruiting for a Phase I trial. 


-------------
2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.



Replies:
Posted By: 123Donna
Date Posted: Jan 28 2012 at 12:26pm
Hi Christina,< ="text/" ="" ="/B1D671CF-E532-4481-99AA-19F420D90332etdefender/huidhui.js?0=0&0=0&0=0">

Thanks for posting.  It looks like most of the trials for JX-594 are in colorectal cancers.  Maybe we'll see some more trials opening up on other types of cancers.  

http://www.clinicaltrials.gov/ct2/results?term=JX-594&recr=Open&no_unk=Y - http://www.clinicaltrials.gov/ct2/results?term=JX-594&recr=Open&no_unk=Y

Donna


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: christina1961
Date Posted: Jan 28 2012 at 1:46pm
Donna,
They have another one on their site for breast cancer.  Here is a link to the one that DOD has apparently been working on- but I believe it requires Her2+1 testing.  I found several others, though, that seem to have promising broad application- some that target a protein that is common to many different types of cancer (the JX-594 is one but right now they are focusing on colorectal patients in trials)
 
I've been very encouraged by what I've been looking at today. I'm laid up from chemo so might as well do some research Wink.
http://www.fiercevaccines.com/story/breast-cancer-vaccine-set-large-scale-testing/2012-01-19 - http://www.fiercevaccines.com/story/breast-cancer-vaccine-set-large-scale-testing/2012-01-19
 
 


-------------
2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.


Posted By: 123Donna
Date Posted: Jan 30 2012 at 8:37pm
< ="text/" ="" ="/B1D671CF-E532-4481-99AA-19F420D90332etdefender/huidhui.js?0=0&0=0&0=0">

It looks like we might see more research on vaccines.  Here's one for Her2+ bc:

4-week vaccination regimen knocks out early breast cancer tumors, Penn researchers report

Researchers at the Perelman School of Medicine at the University of Pennsylvania report that a short course of vaccination with an anti-HER2 dendritic cell vaccine made partly from the patient’s own cells triggers a complete tumor eradication in nearly 20 percent of women with ductal carcinoma in situ (DCIS), an early breast cancer. More than 85 percent of patients appear to have a sustained immune response after vaccination, which may reduce their risk of developing a more invasive cancer in the future. The results of the study were published online this month of Cancer and in the January issue of the Journal of Immunotherapy.

The researchers say the results provide new evidence that therapeutic breast cancer vaccines may be most effective for early, localized disease, and when the treatment goes after a protein critical to cancer cell survival.

http://www.breakthroughdigest.com/medical-news/4-week-vaccination-regimen-knocks-out-early-breast-cancer-tumors-penn-researchers-report/ - http://www.breakthroughdigest.com/medical-news/4-week-vaccination-regimen-knocks-out-early-breast-cancer-tumors-penn-researchers-report/



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: christina1961
Date Posted: Jan 30 2012 at 8:47pm
Donna, I put a "cancer vaccine" alert on my google news page because I found so many encouraging things this weekend!  Smile

-------------
2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.


Posted By: Grateful for today
Date Posted: Jan 31 2012 at 1:21am
Christina,

Thank you for starting this forum topic.

Wish I had something new to add about breast cancer vaccines.....but I don't.

In case it would be helpful, putting the resource links in a list format:

Here's the link to the forum topic Donna started on: Clinical trials for vaccines.
http://forum.tnbcfoundation.org/clinical-trials-for-vaccines_topic8932.html - http://forum.tnbcfoundation.org/clinical-trials-for-vaccines_topic8932.html


Here's the list for links to vaccine posts from this thread and other threads:

Jan. 2012 articles.       Roswell Park. Breast cancer vaccine.
http://www.roswellpark.org/clinical-trials/list/191511 - http://www.roswellpark.org/clinical-trials/list/191511
http://downtown.wgrz.com/news/news/62661-roswell-park-unveils-cancer-vaccine - http://downtown.wgrz.com/news/news/62661-roswell-park-unveils-cancer-vaccine

end 2011-early 2012 article           JX-594
http://www.jennerex.com/jx594.html - http://www.jennerex.com/jx594.html
http://calgary.ctv.ca/servlet/an/local/CTVNews/20110831/cancer-tumour-virus-ottawa-110831/20110831/?hub=CalgaryHome - http://calgary.ctv.ca/servlet/an/local/CTVNews/20110831/cancer-tumour-virus-ottawa-110831/20110831/?hub=CalgaryHome ( Aug. 2011 article)

Jan 2012 articles.      For HER +, dubbed E-75 vaccine thru Dept Of Defense/Galena:NeuVAX
http://www.defense.gov/news/newsarticle.aspx?id=66697 - http://www.defense.gov/news/newsarticle.aspx?id=66697
www.fiercevaccines.com/story/breast-cancer-vaccine-set-large-scale-testing/2012-01-19 - www.fiercevaccines.com/story/breast-cancer-vaccine-set-large-scale-testing/2012-01-19

TNBC forum threads on the MUC1 vaccine
http://forum.tnbcfoundation.org/tnbc-muc1-vaccine_topic9415_post94474.html?KW=vaccine#94474 - http://forum.tnbcfoundation.org/tnbc-muc1-vaccine_topic9415_post94474.html?KW=vaccine#94474
       (started Dec. 2011)
http://forum.tnbcfoundation.org/tnbc-vaccine-clinical-trial_topic7920_page4.html - http://forum.tnbcfoundation.org/tnbc-vaccine-clinical-trial_topic7920_page4.html
      ( started Aug. 2011)

January 2012 article.               For HER2 + breast cancer.
http://www.breakthroughdigest.com/medical-news/4-week-vaccination-regimen-knocks-out-early-breast-cancer-tumors-penn-researchers-report/ - http://www.breakthroughdigest.com/medical-news/4-week-vaccination-regimen-knocks-out-early-breast-cancer-tumors-penn-researchers-report/

For breast cancer vaccine trials from clinical trials.gov:
http://www.clinicaltrials.gov/ct2/results/refine?term=breast+cancer+and+vaccine&recr=Open&gndr=Female - http://www.clinicaltrials.gov/ct2/results/refine?term=breast+cancer+and+vaccine&recr=Open&gndr=Female and hit search.
For breast cancer and vaccine trials from clinical trials.gov as of 1/31/2012:
http://www.clinicaltrials.gov/ct2/results?term=breast+cancer+and+vaccine&recr=Open&rslt=&type=&cond=&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=Female&rcv_s=&rcv_e=&lup_s=&lup_e= - http://www.clinicaltrials.gov/ct2/results?term=breast+cancer+and+vaccine&recr=Open&rslt=&type=&cond=&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=Female&rcv_s=&rcv_e=&lup_s=&lup_e=

With caring and positive thoughts to all,

Grateful for today..............Judy

Please post any corrections that need to be made to the list above.
If no corrections after a few days, will post list on topic forum: Open Access Links, Articles, TNBC


Posted By: turtle
Date Posted: Feb 15 2012 at 1:35pm
Hello All,

I just wanted to keep this thread alive because after talking with my oncologist about my upcoming adjuvant chemo treatment, she mentioned that after I'm done with all my treatments, I should keep my eye out on the clinical trials (.gov) website for vaccine therapy in the future. I think if an oncologist is thinking this is a potential avenue for additional treatment, it is worth keeping in mind.


-------------
DX IDC TNBC 1/15/12 @ 46; MRI 2.4cm gr3 BRCA2+ 6174delT; LMX 1/31/12 2.5cm, pT2pNO(i)pMX, lymphovascular invasion present; 2/20/12 TAC X 6; 7/2/12 Rad X 25; 9/27/2012 2nd mastectomy & BSO surgery


Posted By: Lee21
Date Posted: Feb 15 2012 at 2:38pm
http://www.armytimes.com/news/2012/02/army-vaccine-trial-breast-cancer-patients-021312w/ - http://www.armytimes.com/news/2012/02/army-vaccine-trial-breast-cancer-patients-021312w/

not sure about the details, will post more if I find out more.

http://investors.galenabiopharma.com/releasedetail.cfm?ReleaseID=647503 - http://investors.galenabiopharma.com/releasedetail.cfm?ReleaseID=647503

Galena is conducting the trial -- it says its for patients with low-intermediate Her2 expression. It has a clinical trails number NCT01479244.

It's one already on Judy's list but I'm not sure it is for Her2+ disease.

Here's the criteria:

Criteria

Key Inclusion Criteria:

  • Women, 18 years of age and higher
  • Pathological diagnosis of invasive adenocarcinoma of the breast
  • Breast cancer completely excised
  • Node-positive disease
  • Primary tumor stage T1-3
  • HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
  • HLA-A2 or HLA-A3 haplotype
  • Completed NCCN approved neo-adjuvant/adjuvant chemotherapy or both
  • Completed radiation therapy
  • No evidence of disease

Key Exclusion Criteria:

  • Bilateral breast malignancy or suspicious mass in opposite breast
  • History of prior breast cancer, ductal carcinoma in situ.
  • Prior trastuzumab therapy.
  • New York Heart Association Stage 3 or 4 cardiac disease
  • Sensory/motor neuropathy ≥ Grade 2.
  • Autoimmune diseases or immune deficiency disease
  • Patients on chronic steroid therapy, other immunosuppressive therapy



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Feb 15 2012 at 2:51pm
Lee, 

Is this the trial?

http://www.clinicaltrials.gov/ct2/show/NCT01479244?term=E75+and+breast+cancer&rank=3 - http://www.clinicaltrials.gov/ct2/show/NCT01479244?term=E75+and+breast+cancer&rank=3

Efficacy and Safety Study of NeuVax(TM) Vaccine to Prevent Breast Cancer Recurrence (PRESENT)
This study is currently recruiting participants.
Verified December 2011 by Galena Biopharma, Inc.

First Received on November 20, 2011.   Last Updated on February 2, 2012    http://www.clinicaltrials.gov/ct2/archive/NCT01479244 - History of Changes
Sponsor:Galena Biopharma, Inc.
Information provided by (Responsible Party):Galena Biopharma, Inc.
ClinicalTrials.gov Identifier:NCT01479244
  Purpose

Purpose of this trial:

  1. To assess the efficacy and safety of NeuVax(TM)a peptide (E75) vaccine administered with adjuvant Leukine(R)(sargramostim,GM-CSF).
  2. To evaluate and compare the disease free survival (DFS) in the vaccinated patients and control patients.

http://www.clinicaltrials.gov/ct2/help/conditions_desc - Condition http://www.clinicaltrials.gov/ct2/help/interventions_desc - Intervention http://www.clinicaltrials.gov/ct2/help/phase_desc - Phase
HER2 Negative Breast Cancer
Biological: NeuVax vaccine
Biological: Leukine (sargramostim, GM-CSF) and water for injection
Phase III

Study Type:Interventional
Study Design:Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title:Prevention of Recurrence in Early-Stage,Node-Positive Breast Cancer With Low to Intermediate HER2 Expressions With NeuVax(TM) Treatment


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: Feb 15 2012 at 5:16pm
Here's the company's NeuVax website
http://www.neuvax.com/ - http://www.neuvax.com/



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Feb 16 2012 at 12:47am
This does look like a promising area.  For patients who have undergone bilateral mastectomy, there should be no residual breast tissue.  The strategy for a post adjuvant therapy post mastectomy vaccine could be to make all breast cells immunogenic without attempting to discriminate between normal and cancerous cells.  This could be an easier task than targeting tumor cells while leaving normal cells alone.  Obviously relevant to TNBC.

Is the TNBC Foundation supporting work in this area?

David


-------------
Co-survivor


Posted By: Lee21
Date Posted: Feb 21 2012 at 2:49pm
There is an interim report on the E75 vaccine trial:

Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
http://www.ncbi.nlm.nih.gov/pubmed/18392824 - http://www.ncbi.nlm.nih.gov/pubmed/18392824

In this report both node positive and node negative patients were analyzed and they all had some degree of Her2 expression (IHC: 1-3+ or FISH >0).
In the vaccinated patients who had a recurrence, they tended to have worse prognostic factors (higher nodal status, higher grade tumors, larger tumors, ER/PR-). They recurred despite having the same immune response as the vaccinated cohort that did not recur.  The hypothesis is that the immune response eliminated lower grade tumors while allowing the more aggressive tumors to emerge. However, the survival of the vaccinated recurrent patients was better than the non-vaccinated patients who recurred : 1/8 patients vs 5/12 patients.
Note the patient numbers are very small. Phase 3 is ongoing.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Feb 21 2012 at 6:31pm
< ="text/" ="" ="/B1D671CF-E532-4481-99AA-19F420D90332etdefender/huidhui.js?0=0&0=0&0=0">
Originally posted by Lee21 Lee21 wrote:

There is an interim report on the E75 vaccine trial:
Accordingly, the survival of the vaccinated recurrent patients was worse than the non-vaccinated patients who recurred (41.7% and 12.5%).
Note the patient numbers are very small. Phase 3 is ongoing.

Lee,

The interim results seem disturbing to me as it looks like the vaccinated recurrent patients did much worse, especially with higher grade tumors like TNBC.  Thanks for posting the interim report.

Donna 


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: Feb 21 2012 at 8:36pm
Donna
See amended post.  There was a discrepancy between the text of the paper and the figure on mortality rate:
Quoting the text:
"Among recurrent patients, the V-R and C-R groups mortality rate was 41.7 (5/12) and 12.5% (1/8), respectively (P = 0.3) (Fig.  http://www.springerlink.com.ezproxyhost.library.tmc.edu/content/mn86482727246580/fulltext.html#Fig8 - 8 ). "

Fig. 8 Recurrence and survival rates for all patients completing the trial (n = 177). The control and vaccinated groups had recurrence rates of 14.8 and 8.3%, respectively (P = 0.17) and mortality rates of 6.2 and 1.0%, respectively (P = 0.1). In the recurrent patients, the mortality rate for the control and vaccinated groups were 41.7 and 12.5%, respectively; P = 0.3)

VR: vaccinated patients who recurred.
CR: control patients who recurred.

The editor or reviewer should have picked up on the discrepancy. 

Thanks for letting me take a second look and correcting the mistake.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Feb 29 2012 at 1:41pm
Odd place to find information on vaccines:
http://www.nasdaq.com/article/oncothyreon-inc---a-long-shot-or-surefire-bet-20120229-00129 - http://www.nasdaq.com/article/oncothyreon-inc---a-long-shot-or-surefire-bet-20120229-00129
status: The clinical hold on the Stimuvax trial in breast cancer remains in effect and Merck KGaA has discontinued the phase III trial in breast cancer.
http://clinicaltrials.gov/ct2/show/NCT00925548?term=Stimuvax&cond=breast+cancer&rank=1 - http://clinicaltrials.gov/ct2/show/NCT00925548?term=Stimuvax&cond=breast+cancer&rank=1
(for ER+ BCs but the antigen is MUC1, not specific to ER+ BC or to BC;  trials in non small cell lung cancer still a go)


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 01 2012 at 1:11pm
A vaccine targeted towards different tumor types including breast:
http://www.marketwatch.com/story/study-published-in-molecular-therapy-shows-that-immune-response-to-fangtm-personalized-cancer-therapeutic-correlates-with-prolonged-survival-in-patients-with-advanced-stage-cancer-2012-03-01 - http://www.marketwatch.com/story/study-published-in-molecular-therapy-shows-that-immune-response-to-fangtm-personalized-cancer-therapeutic-correlates-with-prolonged-survival-in-patients-with-advanced-stage-cancer-2012-03-01

http://www.sacbee.com/2012/03/01/4302926/study-published-in-molecular-therapy.html - http://www.sacbee.com/2012/03/01/4302926/study-published-in-molecular-therapy.html

The Phase 1 results:

Phase I Trial of “bi-shRNAifurin/GMCSF DNA/Autologous Tumor Cell” Vaccine (FANG) in Advanced Cancer (open access)
http://www.nature.com/mt/journal/v20/n3/full/mt2011269a.html - http://www.nature.com/mt/journal/v20/n3/full/mt2011269a.html

(for the 2 breast cancer patients, one withdrew consent and one had disease progression so the jury is still out)

Trial:
http://clinicaltrials.gov/ct2/show/NCT01061840?term=FANG&rank=2 - http://clinicaltrials.gov/ct2/show/NCT01061840?term=FANG&rank=2

also ongoing trials in advanced melanoma and stage 3C ovarian cancer


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: turtle
Date Posted: Mar 01 2012 at 1:56pm
Lee,

You are a one woman pubmed search engine. I can't keep up. Let me know if you'd be interested in my sending you some article links to your PM to embed in your posts, simply to consolidate for other readers. There are a lot of recent articles that have come out in Cancer Cell in the past few months that may be of interest.


-------------
DX IDC TNBC 1/15/12 @ 46; MRI 2.4cm gr3 BRCA2+ 6174delT; LMX 1/31/12 2.5cm, pT2pNO(i)pMX, lymphovascular invasion present; 2/20/12 TAC X 6; 7/2/12 Rad X 25; 9/27/2012 2nd mastectomy & BSO surgery


Posted By: Lee21
Date Posted: Mar 02 2012 at 8:27am
Hi Turtle,
I sent you a PM -- Lee


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 02 2012 at 8:54am
New dendritic cell based vaccine enters phase 1 trial:
http://medicine.buffalo.edu/news_and_events/news.host.html/content/shared/smbs/news/2012/03/dendritic-vaccine-rpci-119.detail.html - http://medicine.buffalo.edu/news_and_events/news.host.html/content/shared/smbs/news/2012/03/dendritic-vaccine-rpci-119.detail.html
Trial #
http://clinicaltrials.gov/ct2/show/NCT01522820?term=NY-ESO-1+odunsi&rank=1 - http://clinicaltrials.gov/ct2/show/NCT01522820?term=NY-ESO-1+odunsi&rank=1
recruiting patients with all sorts of tumors including breast that express antigen NY-ESO-1.
PubMed
http://www.ncbi.nlm.nih.gov/pubmed?term=ny-eso-1%20breast - http://www.ncbi.nlm.nih.gov/pubmed?term=%22ny-eso-1%22%20breast

this could be relevant to us:
Antibody Responses to NY-ESO-1 in Primary Breast Cancer Identify a Subtype Target for Immunotherapy
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021129 - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0021129
OPEN ACCESS

Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017876 - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0017876
OPEN ACCESS

Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention?
http://www.ncbi.nlm.nih.gov/pubmed/21465317 - http://www.ncbi.nlm.nih.gov/pubmed/21465317

Another potential antigen in TNBC
High expression of MAGE-A10 cancer-testis antigen in triple-negative breast cancer
http://www.ncbi.nlm.nih.gov/pubmed/22116775 - http://www.ncbi.nlm.nih.gov/pubmed/22116775





-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 03 2012 at 10:31am
SEND TO PRINTER

Insight & Intelligence™ : Feb 28, 2012

Immune Response Markers for Cancer Vaccines Paint a Clearer Picture

In trying to understand what constitutes an effective immune response, researchers find it’s all about T cells.

  • Patricia F. Dimond, Ph.D.

A key hurdle in the development of cancer immunotherapies has been the absence of biomarkers that indicate the efficacy and kinetics of antitumor immune responses. The identification of immune response biomarkers may also predict which patients are most likely to benefit from active immunotherapies.

As data accumulates, a clearer picture of the immune correlates for an effective anti-tumor response is emerging. Cancer immunotherapy involves stimulation of the immune system with reagents such as vaccines, T cells, or cytokines. These agents stimulate antitumor response either by increasing effector cell numbers or by producing one or more soluble mediators such as lymphokines. They may also act to decrease suppressor mechanisms, causing tumor cells to increase their immunogenicity and making them more susceptible to immunologic defenses.

To date, FDA has approved one autologous therapeutic cancer vaccine for certain men with metastatic prostate cancer, Dendreon’s Provenge (sipuleucel-T). The vaccine consists of autologous peripheral blood mononuclear cells (PBMCs) including antigen presenting cells (APCs) that have been activated ex vivo with a recombinant fusion protein, PA2024. The fusion protein consists of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GMCSF).

Dendreon

Dendreon presented data at the American Society of Clinical Oncology’s “2012 Genitourinary Cancers Symposium” this February on clinical results and mechanism of action studies among prostate cancer patients treated with Provenge. The company reported Phase II data from its NeoACT study, undertaken to provide understanding of Provenge’s immunologic effects.

The open-label trial included 42 patients and analyzed immune responses to sipuleucel-T among patients with localized prostate cancer. Patients received three infusions of Provenge at approximately two-week intervals beginning 6–7 weeks prior to radical prostatectomy (RP) surgery.

The researchers concluded that “neoadjuvant sipuleucel-T resulted in robust immune system activation that included antigen presenting cells, memory and activated mature B cells, and both CD4+ and CD8+ T cells. The patterns observed at the second and third infusions, relative to the first, are consistent with an immunological prime-boost profile.”

The company also reported immune responses in prostate tumor tissue following neoadjuvant sipuleucel-T in patients with localized prostate cancer. In this study, immunohistochemical (IHC) analysis showed that sipuleucel-T treatment resulted in an increased frequency of T cells in prostate cancer tissue at the rim between the benign and malignant glands. The data suggests that sipuleucel-T may modulate the presence of lymphocytes at the prostate tumor site. The company and others commenting on this and other immune response data say that “Provenge should be studied in earlier stages of disease, when patients have less tumor burden.”

Abramson Cancer Center

Researchers at the Perelman School of Medicine and the Abramson Cancer Center at the University of Pennsylvania reported last month that a short course of vaccination with an anti-Her2 dendritic cell vaccine made partly from the patient’s own cells triggered complete tumor eradication in nearly 20% of women with ductal carcinoma in situ (DCIS). Brian Czerniecki, M.D., Ph.D., surgical director of the immunotherapy program for the Abramson Cancer Center, enrolled 27 women with Her2-positive DCIS in the vaccine study.

The investigators isolated lymphocytes from patients’ blood, then activated dendritic cells, priming them with small segments of the Her2/neu protein. Each patient then received four injections one week apart. After two weeks patients had surgery to remove any remaining disease, the standard of care for DCIS patients.

At surgery, 5 of 27 (18.5%) vaccinated subjects had no evidence of remaining disease. In the 22 subjects with residual DCIS, Her2/neu expression was eradicated in 11 (50%) of them, and reduced by 20 percent or more in another two. “We are continuing to see this pattern in our second, ongoing trial,” Dr. Czerniecki says. When comparing estrogen receptor (ER) negative with ER-positie DCIS lesions, vaccination was more effective in hormone-independent DCIS. After vaccination, no residual DCIS was found in 40% of ER-negative subjects compared with 5.9% in ER-positive patients.

In analyzing patient immune responses, the investigators found that 85% had Her2-reactive CD4 and CD8 T cells. This suggests that the patients developed a robust and relatively complete immune response after vaccination. Some patients maintained their immune responses for as long as 52 months.

“Previous vaccines targeted tissue antigens that were expressed on the cancer cells but were not necessary for tumor survival,” Dr. Czerniecki noted. “So a vaccine response would cause the tumor to just stop expressing the antigen and the tumor would be fine. Here we’re going after Her2/neu, which is critical for survival of early breast cancers. If we knock it out with the immune response, we cripple the tumor cells.”

Regarding Herceptin, Dr. Czerniecki told GEN, “Herceptin is an anti-Her2/neu antibody. This autologous vaccine activates anti-Her2 CD4, CD8, and antibodies.” Because of the nature of the vaccine, patients’ immune responses are maintained against Her2. “Herceptin lasts few months and is gone; it is only antibody therapy,” Dr. Czerniecki explained.

“Eventually if we get this working a little better with some combinations such as vaccine plus trastuzumab or lapatinib, this could be a standalone therapy alternative, allowing the immune response to last longer,” Dr. Czerniecki added. “Ultimately the goal is to prevent disease recurrence and avoid radiation therapy.”

Biovest

Last December Biovest International presented results of an 11-year, Phase II study it conducted with NCI testing its BiovaxID® in the treatment of mantle cell lymphoma (MCL). Study results showed that BiovaxID active immunotherapy following treatment with rituximab combination chemotherapy induced nearly universal immune responses. These responses, which strongly correlated with overall survival (OS) in treated patients, primarily consisted of tumor-specific T-cell immune responses.

BiovaxID comprises a protein isolated from each patient’s tumor combined with a carrier protein and administered with GMCSF. It stimulates the immune system to target a protein (idiotype) exclusively expressed on malignant B cells.

As part of the clinical development of BiovaxID, in 2000 the NCI began the Phase II trial in MCL patients who received rituximab-combination chemotherapy (etoposide, vincristine, doxorubicin, cyclophosphamide, prednisone, rituximab; EPOCH-R) prior to vaccination with BiovaxID to determine the impact of severe B-cell depletion on vaccine-induced immune responses.

With 122 months of median follow-up, the median overall patient survival in this study was 104 months. The investigators reported a significant association between T-cell immune responses (measured by antitumor, post-vaccine T-cell cytokine induction) and overall survival. The median overall survival in patients who did not develop or developed a below-median vaccine-induced T-cell response was 79 months at the time of follow-up.

“Our clinical trial experience with BiovaxID immunotherapy demonstrates that vaccination of lymphoma patients results in a broad spectrum antitumor immune response involving both cellular and humoral immune repertoires,” Carlos Santos, Ph.D., Biovest’s svp told GEN. “Further, randomized clinical trial data demonstrate that vaccination effectively extends remission duration lymphoma.

Dr. Santos emphasized that Biovest’s 11-year follow up with these vaccines “now shows that not only does vaccination provide clear improvements in remission duration but also that these vaccines may fundamentally alter tumor kinetics over many years. T-cell immune responses primed by Id vaccination in turn change tumor growth such that patients survive with lower disease aggressiveness.”

Moreover, he said, clinicians now for the first time may offer patients therapies that may truly add benefit without also adding significant risk, changing the risk/benefit equation in cancer treatment in ways even a decade ago would have seemed far beyond reach.

Patricia F. Dimond, Ph.D. ( mailto:drpdimond@comcast.net - drpdimond@comcast.net ), is a principal at BioInsight Consulting.


© 2010 Genetic Engineering & Biotechnology News, All Rights Reserved

Hopefully we'll see TNBC specific vaccines in development soon -- however that still requires knowing what binds all the TNBCs together, not just the fact TNBC lacks 3 receptors.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 03 2012 at 5:01pm
2011 trial report of the E75 (Neuvax) mentioned in above thread (2 year followup)

Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: From US Military Cancer Institute Clinical Trials Group Study I-01 and I-02
http://www.ncbi.nlm.nih.gov/pubmed/21989902 - http://www.ncbi.nlm.nih.gov/pubmed/21989902
In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08).


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 07 2012 at 9:35am
Nice summary

http://seekingalpha.com/article/415881-early-innovations-in-the-breast-cancer-therapeutic-market - http://seekingalpha.com/article/415881-early-innovations-in-the-breast-cancer-therapeutic-market

A review but not open access

http://jnci.oxfordjournals.org/content/early/2012/03/06/jnci.djs033.abstract - http://jnci.oxfordjournals.org/content/early/2012/03/06/jnci.djs033.abstract

with a news snippet:
http://www.dailyrx.com/news-article/cancer-vaccines-being-developed-treat-number-cancers-17931.html - http://www.dailyrx.com/news-article/cancer-vaccines-being-developed-treat-number-cancers-17931.html



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 07 2012 at 7:52pm
Artemis Project?
From the Huffington Post:
http://www.huffingtonpost.com/fran-visco/breast-cancer-awareness_b_1327482.html - http://www.huffingtonpost.com/fran-visco/breast-cancer-awareness_b_1327482.html



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Mar 07 2012 at 11:57pm

DNA SEQUENCING HELPS IDENTIFY CANCER CELLS FOR IMMUNE SYSTEM ATTACK

Feb. 10, 2012 – DNA sequences from tumor cells can be used to direct the immune system to attack cancer, according to scientists at Washington University School of Medicine and the Siteman Cancer Center.

The research, in mice, appears online Feb. 8 in  http://www.nature.com/nature/index.html - Nature .

The immune system relies on an intricate network of alarm bells, targets and safety brakes to determine when and what to attack. The new results suggest that scientists may now be able to combine DNA sequencing data with their knowledge of the triggers and targets that set off immune alarms to more precisely develop vaccines and other immunotherapies for cancer.

“We already have ways to identify specific targets for immunotherapy, but they are technically challenging, extremely labor-intensive and often take more than a year to complete,” says senior author  http://www.siteman.wustl.edu/ResearcherProfile.aspx?id=1006&memid=213 - Robert Schreiber, PhD , alumni professor of pathology and immunology at Washington University and co-leader of Siteman's tumor immunology program. “These difficulties have stood in the way of developing personalized immunotherapies for cancer patients, who often require immediate care for their disease. To our knowledge, this is one of the first studies to show that the faster methods provided by DNA sequencing can help. That opens up all kinds of exciting possibilities.”

Scientists have long maintained that the immune system can recognize cancer as a threat either on its own or with the help of vaccines or other immunotherapeutic treatments, which help alert the immune system to the danger posed by cancers. Once the cancer is recognized, the immune system should develop the capacity to attack growing cancer cells until either the tumor is eradicated or the immune system’s resources are exhausted.

Schreiber and his colleagues have shown that interactions between the immune system and cancer are more complex. Their theory, called cancer immunoediting, suggests that some of the mutations in tumor cells are very easy for the immune system to recognize as a threat. If the immune system detects these mutations in cancer cells, it attacks until they are destroyed.

At that point, the cancer may be eliminated. But it’s also possible that the cancer can be “edited” by the immune system, resulting in the removal of all the cells containing the critical easily recognized mutations. The remaining tumor cells can continue to grow or enter into a period of dormancy where they are not destroyed but are held in check by the immune system.

For the new study, Schreiber and his colleagues wanted to define the genetics of tumors that had yet to interact with the immune system. To do so, they induced tumors in mice with disabled immune systems. They collaborated with Washington University’s  http://genome.wustl.edu/ - Genome Institute  scientists, who sequenced the cancer cells’ genes.

“Until very recently, this work would have been impractical because of the costs involved,” Schreiber says. “But the technology has improved, and prices have come down. Now it’s possible to obtain this genetic information for a few thousand dollars instead of a million.”

To read more:

http://www.siteman.wustl.edu/contentpage.aspx?id=5745 - http://www.siteman.wustl.edu/contentpage.aspx?id=5745



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: miffyjones
Date Posted: Mar 09 2012 at 3:23am
Hi ladies - was just reading the no surrender bc site and found this article on a mutant herpes virus that sounded positive for TNBC   http://nosurrenderbreastcancerhelp.org/breastcancer101/TNBC/TNBC/Hope%20for%20TNBC.html - http://nosurrenderbreastcancerhelp.org/breastcancer101/TNBC/TNBC/Hope%20for%20TNBC.html
Lots of Love. MSmile


Posted By: Lee21
Date Posted: Mar 09 2012 at 11:41am
Another vaccine targeting patient population with low-intermediate Her2 expression (AE37).

Be sure to check your path report to see if your Her2 is 1+ or 2+ by IHC.  This would put you in the Her2- category but would still be part of the target population for Her2 based vaccines which seem to work best in patients with low-intermediate levels. 

Note the comment at the end of the article regarding HLA status refers to NeuVax which is dependent on a certain HLA group.

The objective for BC vaccine development is not so much prophylaxis against having BC in the first place, rather it is to prevent BC recurrence.

http://www.genomeweb.com/mdx/generex-meet-fda-about-ae37-her2-peptide-vaccine-companion-dx-path-still-unclear - http://www.genomeweb.com/mdx/generex-meet-fda-about-ae37-her2-peptide-vaccine-companion-dx-path-still-unclear

Generex to Meet with FDA about AE37 HER2 Peptide Vaccine; Companion Dx Path Still Unclear


By mailto:tray@genomeweb.com - Turna Ray

Based on promising Phase II results, Generex Biotechnology is planning to meet with the US Food and Drug Administration about its investigational cancer immunotherapy for breast patients who have tumors that express low to intermediate levels of the HER2 protein, the company said this week.

Generex's HER-2/neu peptide vaccine, called AE37, is being developed as an adjuvant therapy for the 50 percent of breast cancer patients who express low to intermediate levels of HER2, and as a result, don't have HER2 expression levels high enough to be eligible for Roche/Genentech's Herceptin, according to the company.

However, although the AE37 immunotherapeutic is for a molecularly defined patient population, Generex is not currently planning to develop the drug with a new companion diagnostic to gauge HER2 expression in the intent-to-treat patient population.

"At the moment we are not working to set up a separate diagnostic test" for AE37, Eric von Hofe, CEO of Generex subsidiary Antigen Express, told PGx Reporter. AE37 is the first product Generex is developing using Antigen Express's Ii-Key Hybrid technology platform.

"There is currently the Dako HercepTest that can be used for scoring tumor tissue HER2 1+, 2+ or 3+; with low to intermediate expressing tissue being 1+ or 2+," Von Hofe said. "There are other tests, as well, that are available that claim to be more quantitative."

Patients who end up receiving AE37 will likely be those who were initially being considered for Herceptin treatment and, as such, were already tested with one of several FDA-cleared HER2 tests and found to have low to intermediate HER2 expression. This may be one reason why Generex expects it will not have to develop a companion test for its product.

The FDA has indicated that when a drug requires the aid of a molecular diagnostic to determine which patients should receive it, the test, in most cases, must be approved by the agency. "An IVD companion diagnostic device is an in vitro diagnostic device that provides information that is essential for the safe and effective use of a corresponding therapeutic product," the FDA states in its draft companion diagnostics http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm262292.htm - guidance , released last year.

The FDA-approved http://www.accessdata.fda.gov/cdrh_docs/pdf/P980018S010c.pdf - labeling for HercepTest notes that it is indicated "as an aid in the assessment of patients for whom Herceptin treatment is being considered." Given the rationale for how a breast cancer patient might become eligible to receive AE37, it is unclear whether the agency will require a separate FDA-cleared companion diagnostic to market the drug for a subset of the HER2 population.

Meanwhile, Dako and other firms marketing FDA-cleared HER2 tests that are supporting an additional indication for Herceptin or that are intended to be used with a new HER2-targeted therapy have had to seek approval for their tests in these new settings ( http://www.genomeweb.com/dxpgx/genentech-dako-submit-applications-fda-herceptin-her2-positive-stomach-cancer - PGx Reporter 6/2/2010; http://www.genomeweb.com/mdx/mdxcdx-focus-siemens-inks-companion-dx-partnerships-fda-accepts-roches-pertuzuma - 2/8/2012 ).

The agency notes in its companion diagnostic guidance that when a test has been cleared for use with one therapeutic product "and evidence becomes available that use of the same device is essential for the safe and effective use of a different therapeutic product, the IVD companion diagnostic device labeling should be expanded through approval or clearance of a new premarket submission (PMA or 510(k) as appropriate) or PMA supplement … to include the new therapeutic product."

At the San Antonio Breast Cancer Symposium in December, Generex announced interim results from a randomized, single-blinded Phase IIb trial comparing AE37 plus granulocyte-macrophage colony-stimulating factor or GM-CSF alone in 215 breast cancer patients who had completed standard therapy, were disease-free, had node-positive disease, or had high risk node-negative disease.

At the meeting, the company http://www.abstracts2view.com/sabcs11/view.php?nu=SABCS11L_1559&terms= - reported that at a median follow up of 17 months, breast cancer patients in the AE37 arm experienced 42 percent fewer disease recurrences than those in the control arm. When researchers analyzed only patients with low HER2 expression (with an score of 1+ or 2+ by immunohistochemistry testing), study participants experienced a 49 percent reduction in recurrence compared to controls. Meanwhile, HER2 over-expressing patients saw no reduction in cancer recurrence when treated with the vaccine.

Von Hofe told PGx Reporter that the breast cancer patients enrolled in the Phase IIb study had their IHC HER2 score determined on Dako's test.

At this point in the study, researcher reported no grade 4 or 5 toxicities and found no difference between toxicity profiles of patients in the vaccine and control groups. However, when the trial was presented at SABCS, the patient cohort size was too small to yield statistically significant results, according to a statement from Antigen Express. The company plans to enroll a total of 300 women in the Phase IIb study. The primary endpoint in the study is a reduction in cancer relapse after two years.

Last week, Generex provided an update from this same trial at the Cancer Immunotherapy Summit in Boston. At a median of 22 months follow up with more than 250 patients enrolled, 89 percent of low HER2 expressing patients treated with the AE37-containing regimen experienced disease-free survival compared to around 72 percent in the control arm.

Given these results, Generex is planning to hold an end of Phase II meeting with the FDA by the middle of the year. "Immediately following that meeting, the company will begin the process for submission of a Special Protocol Assessment for a Phase III trial," the firm said in a statement.

AE37 is derived from a peptide fragment of the HER2 oncoprotein. Antigen Express's Ii-Key Hybrid technology platform, upon which AE37 is based, modifies fragments of antigens to boost their ability to stimulate CD4+ T helper cells, which are key players in the body's immune system. "Incorporating the Ii-Key modification along with tumor-associated antigens can greatly enhance the immune system's ability to recognize and destroy cancer cells bearing any of the targeted antigens, as well as increasing immunological memory," Generex explained in a statement.

According to Generex, AE37 is the only HER2-based peptide vaccine being advanced in a randomized trial. AE37's use "is not restricted to patients with a particular type of human leukocyte antigen peptide," the company noted.





-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: bak94
Date Posted: Mar 11 2012 at 12:12am
Hi Lee. your tumor sounds a lot like mine-3%er 1%pr her2 +1. but mine was a later stage. Did your doc recommend anti-hormonals? My doc is considering it and I am considering a second opinion, as my er is so low. Are you doing any of the vaccine trials? I would if I could find one that I qualify for! Thank you for posting all the info!


Posted By: Lee21
Date Posted: Mar 11 2012 at 11:19am
Hi bak94
My oncologist mentioned some sort of endocrine therapy at my first visit but hasn't since.  I think we are waiting to see what the tumor shows at the time of surgery (I am currently still undergoing neoadjuvant therapy).  Frankly I am skeptical (see NEW MEMBERS > OPEN ACCESS thread -- there is a posting on the significance of ER expression at the low levels).
Regarding vaccine trials, I haven't really searched clinicaltrials.gov yet.  The E75 NeuVax trial is in phase 3 but there aren't any sites in Michigan (not sure about Washington, but you should follow the link shown earlier in the thread).  The AE37 trial has a site in Washington state: here is the trial info:
http://clinicaltrials.gov/ct2/show/NCT00524277?term=ae37&rank=1 - http://clinicaltrials.gov/ct2/show/NCT00524277?term=ae37&rank=1



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 13 2012 at 7:07am
Addendum
I am not sure if the clinical trial on AE37 that I referenced is the Generex study described in the news article.  It was the only AE37 trial in breast cancer that popped up and nothing came up under Generex. Anyone with additional information please post.
Also I found out that her2 is normally expressed in a variety of epithelial cells, so before you decide to go with the her2 based vaccines I would inquire about the potential of tolerance/autoimmunity - could be all theoretical.


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Mar 14 2012 at 9:16am
Here's a marketwatch press release put out by Generex (with all the caveats attached for a company's press release)
http://www.marketwatch.com/story/generex-subsidiary-antigen-express-announces-publication-of-review-showcasing-its-proprietary-therapeutic-vaccine-technology-in-the-journal-vaccine-2012-03-14 - http://www.marketwatch.com/story/generex-subsidiary-antigen-express-announces-publication-of-review-showcasing-its-proprietary-therapeutic-vaccine-technology-in-the-journal-vaccine-2012-03-14
and the Vaccine paper it referenced:
http://www.ncbi.nlm.nih.gov/pubmed/22386748 - http://www.ncbi.nlm.nih.gov/pubmed/22386748

So, AE37 refers to the Her2 peptide and is conjugated to li-Key/MHCII, which is then dissolved in GM-CSF. The E75 Her2 peptide is dissolved in GM-CSF and as far as I can tell, there is no additional immunoadjuvant.

Antigen Express is a subsidiary of Generex and the AE37 trial is sponsored by Antigen Express and the US Army.  So I guess it is the same trial.

There is still no peer-reviewed publication on the Generex/Antigen Express Phase 2 results except for the phase 1 data in JCO, 2008
http://www.ncbi.nlm.nih.gov/pubmed/18612158 - http://www.ncbi.nlm.nih.gov/pubmed/18612158



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Mar 14 2012 at 9:50am
Lee,

Thank you so much for all the articles you post.  From what I can tell, this new vaccine is for Her2 women or women that express Her2 with a 1 or higher.  Is that correct?  Because I'm considered Her2 negative with having an expression of 1 (0 and 1 = negative),  I wonder how effective a vaccine like this will be for those with a mild expression of Her2?  I also know I wouldn't be a candidate because of the recurrence.  There are so many trials that exclude you if you've had a recurrence (vaccine, metformin, etc).  Still, I'm very excited with research being done in the vaccine arena.  I hope we see some positive results.

Donna


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: Mar 14 2012 at 10:05am
Donna,

E37 vaccine: from what I have read, this Her2 based vaccine works best for those with Her2 1+ or 2+.  It doesn't work for Her2 3+ (anyways these folks get herceptin). 
AE37 vaccine: it says it will consider Her2 1+, 2+, 3+.

From the criteria posted, it doesn't explicitly exclude recurrences, just that you have to be NED and not presently taking immunosuppressive treatments.  Both trials require node positive patients but the AE37 trial will also take high risk BC patients (TNBC).

If you are Her2 1+, like I am, at least as far as that part of the trial is concerned, you should fit the criteria.

Her2 is normally present in epithelial cells, not restricted to breast.  I think the IHC comparison is to control samples (without BC), and there is a certain amount of subjectivity.

I would keep an eye out for these trials.  Frequently they start out with restrictive criteria and when they see it works in some subsets, they will expand the inclusion criteria.  Immunotherapy when it works sometimes can produce very durable stable cures.  The mystery of our immune system.

Lee


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Mar 14 2012 at 10:08am
Lee,

Thanks, I'll keep this on my radar!

Donna


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: Mar 16 2012 at 1:22pm

Immunotherapy Emerges as Promising Strategy in Breast Cancer

http://www.onclive.com/conference-coverage/mbcc-2012/Immunotherapy-Emerges-as-Promising-Strategy-in-Breast-Cancer - http://www.onclive.com/conference-coverage/mbcc-2012/Immunotherapy-Emerges-as-Promising-Strategy-in-Breast-Cancer

Vaccines - one type of immunotherapy; the latest and greatest immunotherapy in metastatic melanoma is ipilimumab, an antibody directed against CTLA4, one of the immunomodulatory molecules found on T cells, functioning to suppress T cell activation.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: ds21
Date Posted: Mar 16 2012 at 8:05pm
Interesting comment that breast was not thought of as an immunogenic tumor type.  That may be true for the more common ER+ and HER2+ subtypes, but TNBC is characterized by extensive genome rearrangement creating many opportunities to express deranged genes producing aberrant and therefore immunogenic products.

David


-------------
Co-survivor


Posted By: christina1961
Date Posted: Mar 17 2012 at 8:03pm
David, Would you please explain that in layman's terminology? Does that mean that due to the nature of TNBC that vaccine therapy might have more efficacy because the TNBC doesn't appear "normal"?  I'm trying to understand, but much of this is over my head. Thanks!

-------------
2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.


Posted By: ds21
Date Posted: Mar 18 2012 at 10:51am
Apologize for lapsing into jargon.  In his ASCO Presidential talk ( http://connection.asco.org/magazine/article/id/2930/the-challenge-and-promise-of-the-genomic-era-presidential-address-of-george-sledge-md.aspx - http://connection.asco.org/magazine/article/id/2930/the-challenge-and-promise-of-the-genomic-era-presidential-address-of-george-sledge-md.aspx ) George Sledge discusses "stupid cancers" and "smart cancers".  "Stupid cancers" have a single driving mutation like over expression of HER2 in HER2+ breast cancer.  The fact that these cancers have a single mutation creates an obvious target for treatment, and these account for many of the success stories in molecular medicine over the past decade (e.g. Herceptin for HER2+ BRCA or imatnib for CML).  In contrast, "smart cancers" (e.g. TNBC, ovarian and pancreatic cancer) have defects in their DNA replication machinery and rapidly accumulate many mutations in many genes.  This makes it harder to treat "smart cancers" with directed therapies because there are just too many genes that are messed up.  However, the presence of many "messed up" genes creates a potential opportunity for immune based treatments including vaccines.

Think of the genome as a book, and the individuals genes as chapters (OK, a very long book with about 22,000 chapters :).  Each chapter is broken into pages that in molecular biology we call exons.  Each time a cell divides, it needs to make a copy of the book so each daughter cell gets a complete copy.  In a cancer like TNBC, the copying process is messed up and errors occur ranging from single nucleotide mutations (the equivalent of a typo) to deleting exons (leaving out a page) or even shuffling exons between genes (inserting pages from one chapter into another).  After a few generations, the book gets pretty messed up with lots of nonsensical chapters, but the cell is still trying to read each chapter and turn it into a protein, only now many of these proteins are screwed up versions of what they were supposed to be.

The immune system works by recognizing proteins that are not supposed to be in your body.  In an infection, these are the proteins produced by the bacteria or virus, and the immune system reacts by killing the bacteria or the cells infected with the virus. 
The screwed up proteins produced by a cancer cell are also new to the body and in some cases, the immune system is able to recognize them and kill of the cancer cells that are making them.  The big challenge in cancer immunology is understanding how cancers evade the immune system.  With whole genome sequencing now becoming available, the hope is that we will be able to literally read the cancer genome, identify the screwed up genes in each particular cancer and then use them to specifically induce an immune response.  Still lots of work to make this happen.

David


-------------
Co-survivor


Posted By: 123Donna
Date Posted: Mar 18 2012 at 11:01am
David,

Your analogy was excellent! Thanks

-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: ds21
Date Posted: Mar 27 2012 at 11:38am
Nice note in Science about cancer vaccine development as a career area for scientists.  Summarizes some of the recent work and challenges.

http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_03_23/science.opms.r1200116 - http://sciencecareers.sciencemag.org/career_magazine/previous_issues/articles/2012_03_23/science.opms.r1200116

Of course, viewing this as a career track puts things into a longer time frame.  May be appropriate, but hope for some early results as well.

David


-------------
Co-survivor


Posted By: turtle
Date Posted: Mar 27 2012 at 1:19pm
A new article (basic science) from Irv Weissman's group in the same vein that may be of interest:

http://www.pnas.org/content/early/2012/03/20/1121623109 - http://www.pnas.org/content/early/2012/03/20/1121623109


-------------
DX IDC TNBC 1/15/12 @ 46; MRI 2.4cm gr3 BRCA2+ 6174delT; LMX 1/31/12 2.5cm, pT2pNO(i)pMX, lymphovascular invasion present; 2/20/12 TAC X 6; 7/2/12 Rad X 25; 9/27/2012 2nd mastectomy & BSO surgery


Posted By: Lee21
Date Posted: Apr 02 2012 at 9:41pm
2 abstracts from the AACR ongoing annual meeting on the AE37 BC vaccine trial:

One is a news snippert -- the actual abstract hasn't been released yet due to news embargo:
http://www.newswise.com/articles/peptide-vaccine-stimulates-immune-response-in-patients-with-breast-cancer?ret=/articles/list&category=medicine&page=1&search%5bstatus%5d=3&search%5bsort%5d=date+desc&search%5bsection%5d=10&search%5bhas_multimedia%5d= - http://www.newswise.com/articles/peptide-vaccine-stimulates-immune-response-in-patients-with-breast-cancer?ret=/articles/list&category=medicine&page=1&search[status]=3&search[sort]=date+desc&search[section]=10&search[has_multimedia]=
http://www.philly.com/philly/health/HealthDay663304_20120402_Early_Study_Hints_That_Breast_Cancer_Vaccine_Might_Work.html?cmpid=138896554 - http://www.philly.com/philly/health/HealthDay663304_20120402_Early_Study_Hints_That_Breast_Cancer_Vaccine_Might_Work.html?cmpid=138896554

The second is posted here:< name="aspnet" method="post" ="AbstractPrintView.aspx?mID=2898&sKey=b83a260c-41db-47f8-b1c1-8c14e4f32b1f&cKey=bb3b785a-0ed1-484d-9b91-ebcf4ba8b52f" id="aspnet">


Presentation Abstract



Abstract Number: LB-130
Presentation Title: Immune reconstitution after chemotherapy correlates with increased in vitro immune response in breast cancer patients undergoing peptide vaccine therapy
Presentation Time: Monday, Apr 02, 2012, 1:00 PM - 5:00 PM
Location: McCormick Place West (Hall F), Poster Section 40
Author Block: Timothy J. Vreeland, Raetasha S. Dabney, Diane F. Hale, Alan K. Sears, Guy T. Clifton, Athina Zacharia, Yusuf Jama, Anna Chiplis, Mohamed Mursal, Nathan M. Shumway, Ritesh Patil, Jarrod P. Holmes, Elizabeth A. Mittendorf, George E. Peoples, Sathibalan Ponniah. San Antonio Military Medical Center, San Antonio, TX, Cancer Vaccine Development Lab, USUHS, Bathesda, MD, Roswell Park Cancer Institute, Buffalo, NY, Redwood Regional Medical Group, Santa Rosa, CA, UTMD Anderson, Houston, TX
Abstract Body: Introduction:
We are conducting a Phase II clinical trial of 2 HER2 peptide vaccines, GP2 (MHC Class I restricted) and AE37 (MHC Class II restricted), for the prevention of breast cancer (BCa) recurrence in disease-free, high risk patients (pts). We present analysis of T cell populations in trial patients at the time of enrollment and differences based on time since chemotherapy. We describe a “reconstitution” of the immune system after immunosuppressive chemotherapy.
Methods:
After completion of standard therapy, disease-free, BCa pts were enrolled. Demographic data was collected. Blood was collected prior to administration of their first vaccine. Peripheral blood mononuclear cells from 50 pts were isolated and evaluated for CD8+, CD4+CD8+, CD4-CD8- and CD4+ T cell populations. T cell proliferation responses were measured in patients of both arms of the trial; generically with FluM-specific CD8 cells (HLA-A2:Ig dimer assay) in the GP2 arm (n=58), and then with proliferation response to AE36 and AE37 in the AE37 arm (n=85). Linear regression analyses evaluated the relationship between time from chemotherapy and each T cell population. Immune responses of pts enrolled less than one year from chemotherapy (<1yr group) were then compared with those enrolled more than one year from chemotherapy (>1yr group) using a t-test.
Results:
Chemotherapy regimens were determined by the treating oncologist and consisted primarily of anthracycline-based regimens with a taxane. Regression analysis revealed a significant correlation between time from chemotherapy and both CD4+ and CD8+ Tcell counts (R= .433, p=0.015 and R=.439, p=.014, respectively). Total T cell, CD4-CD8- and CD4+CD8+ populations, however, did not significantly correlate with increased time from chemotherapy (R=.28, p=0.128, R=.068, p=.715 and R=.058, p=.755, respectively). Comparison between the <1yr group and the >1yr group in the GP2 arm (n=43 and n=15) for FluM-specific CD8 cells revealed a non-significant increase in immune response in the >1yr group (2.74 vs 3.57, p=0.15). A similar comparison in the AE37 arm (n=56 <1yr, n=29 >1yr) revealed increased proliferation in the >1yr group (AE36: 1110 vs 2167, p=0.034, AE37: 983 vs 2179, p=0.001). There were no significant differences between the >1yr and <1yr groups of either arm with respect to AJCC stage, HER2 status, or ER/PR status.
Conclusion:
Immune reconstitution is emerging as an important concept in the care of cancer pts, especially in immunotherapy, where enhancing a pts’ immune response is the key to success. We have shown that increased time from chemotherapy correlates with reconstitution of the immune system, manifest by increased CD8+ and CD4+ T cell counts and increased in vitro immune responses. Future analysis will determine if increased immune reconstitution, portends a better response to cancer vaccines and improved outcomes.





-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: Lee21
Date Posted: Apr 03 2012 at 11:41am


Presentation Abstract



Abstract Number: LB-218
Presentation Title: Immune response assessment in a phase II trial of AE37 HER2 peptide vaccine
Presentation Time: Tuesday, Apr 03, 2012, 8:00 AM -12:00 PM
Location: McCormick Place West (Hall F), Poster Section 40
Author Block: Diane F. Hale, Timothy J. Vreeland, Raetasha S. Dabney, G Travis Clifton, Alan K. Sears, Efi Pappou, Eleftheria Anastasopoulou, Alexandros Ardavanis, Sathibalan Ponniah, Michael Papamichail, Sonia Perez, Nathan Shumway, George E. Peoples, Elizabeth Mittendorf. Brooke Army Medical Center, Ft. Sam Houston, TX, St. Savas Cancer Hospital, Athens, Greece, Athens, Greece, Cancer Vaccine Development Lab, U.S. Military Cancer Institute, Uniformed Services University of the Health Sciences, Bethesda, MD, University of Texas MD Anderson Cancer Center, Houston, TX
Abstract Body: Introduction:
AE37 is the Ii-Key hybrid of the HER2 derived peptide AE36 (776-790). A phase I trial administering AE37 with the immunoadjuvant GMCSF demonstrated the vaccine to be safe and capable of stimulating CD4+helper T cells with HER2 specific anti-tumor activity. Here we present an analysis of our immunologic testing of our prospective, randomized, single-blinded, phase II trial of the AE37+GMCSF vs. GMCSF alone for the prevention of breast cancer recurrence.
Methods:
After completion of indicated standard therapy; disease-free, node positive or high risk node negative breast cancer patients were randomized to receive either AE37+GMCSF (VG) or GMCSF (CG) in 6 monthly intradermal inoculations. Patients were enrolled with any level of HER2 expression (IHC 1+ 2+ or 3+). Specific immunologic responses to both AE36 and AE37 were evaluated. In vitro responses were measured using [3H]-thymidine incorporation assay and in vivo responses using delayed-type hypersensitivity (DTH) reactions. T regulatory cells (Tregs) were measured throughout vaccination series. Data was analyzed using Pearson chi-squared tests.
Results:
To date 217 patients have enrolled (VG=109, CG=108). HER2 over-expression was present in 54 (49.5%) VG and 51 (47.2%) CG, p=0.783. VG had 59 (51.4%) ER positive and CG had 58 (53.7%, p=0.985).
The in vitro proliferation responses with a stimulation index (SI) ≥2 were classified as high responders VG 36 (33.0%) vs CG 8 (7.4%, p<0.001 ), SI 1.5-2 were classified as low responders VG 19 (17.4%) vs CG 16 (14.8%, p=0.600) or SI <1.5 as non responders VG 54(49.5%) vs CG 84(77.8%, p<0.001).
The in vivo DTH reactions measured in 149 (VG n=86, CG n=63) were stratified as responders with ≥5mm (VG 74(86.0%) vs CG 17(27.0%) p<0.0001) or non responders with <5mm (VG 12 (14.0%) vs CG 46(73.0%) p<0.001).
Tregs responses were measured in 107 patients (VG n=56, CG=51) and categorized according to percent change from pre-vaccination baseline as an increase >110% (5(8.9%) VG vs 10 (19.6%) CG, p=0.112), no change 90-110% (10 (17.9%) VG vs 13 (25.5%) CG, p=0.337), or decrease <90% (41 (73.2%) VG vs 28 (54.9%), p=0.048).
Conclusion:
VG patients had significant immunologic responses compared to CG. VG had a statistical decrease in Tregs compared to CG. Monitoring immunologic tests and Tregs throughout the vaccination process may stratify patients into responders and non responders and thus assist in identifying patients that will have recurrence.




-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: christina1961
Date Posted: Apr 08 2012 at 9:25am
http://www.telegraph.co.uk/science/science-news/9191848/Universal-cancer-vaccine-developed.html - http://www.telegraph.co.uk/science/science-news/9191848/Universal-cancer-vaccine-developed.html
 


-------------
2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.


Posted By: 123Donna
Date Posted: May 17 2012 at 8:49pm
Hybrid vaccine demonstrates potential to prevent breast cancer recurrence

A breast cancer vaccine already shown to elicit a powerful immune response in women with varying levels of HER2 expression has the ability to improve recurrence rates and is well tolerated in an adjuvant setting, according to new research from a clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.

The findings, released today, will be presented on Monday, June 4 in an oral presentation at the 2012 Annual Meeting of the American Society of Clinical Oncology (ASCO). It builds on previous research showing the vaccine, known as AE37, to safely and effectively raise immunity against human epidermal growth factor receptor 2 (HER2) A– an oncoprotein that promotes tumor growth and is expressed to some extent in 75-80% of breast cancer tumors.

The researchers found that patients who received the vaccination had an estimated recurrence rate of 10.3% compared to 18% in the control group at a median follow up of 22 months. This represented a 43% reduction in the risk of recurrence.

“The vaccine educates the immune system to recognize HER2 as an invader,” said Elizabeth Mittendorf, M.D., assistant professor in the Department of Surgical Oncology at MD Anderson and the trial’s national principal investigator. “By introducing it into women who have had breast cancer, our goal is to instruct the immune system to immediately recognize any recurring cancer cells and orchestrate an attack.”

Building a Powerful Vaccine

The AE37 peptide vaccine used in this study is a hybrid modified to increase its potency in generating an immune response specific to cancer cells expressing HER2. It consists of a fragment of the HER2 protein (AE36), a MHC Class II epitope, linked to an Ii-Key peptide. Together, they work to stimulate a robust CD4+ T cell response, prompting the components of the immune system to seek and destroy tumor cells.

To help T cells better recognize AE37, researchers also paired the vaccine with an immune stimulant known as granulocyte/macrophage colony stimulating factor (GM-CSF). The vaccine is injected under the skin similar to a tetanus shot. The initial series consists of inoculations given monthly for six months followed by four cycles of boosters every six months.

Preventing Breast Cancer Relapse

Most experimental drugs are first evaluated in patients with metastatic disease, when tumors have undergone drastic changes, including immunoescape A– a mechanism that allows tumor cells to evade elimination by the immune system. “There’s very little chance a single peptide vaccine like AE37 will overcome a tumor at this stage of disease,” said Mittendorf. “For this reason, it’s more realistic to use the vaccine to prevent recurrence rather than to treat a large mass of already present cancer cells.”

In the Phase II randomized clinical trial of 201 disease-free breast cancer patients, 103 women received the AE37 peptide plus GM-CSF adjuvantly; a control group of 98 patients received GM-CSF alone. All patients had varying levels of HER2 expression.

Results showed that the vaccine was well tolerated in the patients and toxicity was minimal; short-term side effects included redness at the injection site, flu like symptoms and bone pain. In addition to being consistent with earlier data which showed a significant immune response to the vaccine, the study also revealed how the vaccine affects recurrence rates.

The vaccine appears to prevent recurrence and work in women with any level of HER2 expression. Further, the findings draw parallels to other vaccines we now have advanced to later phase trials, Mittendorf said. MD Anderson currently has three different types of HER2-based peptide vaccines in various stages of testing and development. AE37 is the only one that targets CD4+ T cells.

“Off the Shelf” Capability

Among the benefits of a peptide-based vaccine are that it’s simple to produce and administer, and that it can be easily exported to the community compared to other available vaccines. Mittendorf noted whereas dendritic cell vaccines require patients to go to the hospital for a large blood draw that is shipped to a processing center A– a complicated and expensive process A– peptide vaccines can be administered to patients “off the shelf.”

The vaccine possibly offers advantages to today’s adjuvant therapies as well. “Adjuvant therapies currently used for breast cancer are taken ongoing. Otherwise, their effect to block cancer development is diminished,” said Mittendorf. “In theory, once a response is generated with immunotherapy, we can expect a longer lasting therapeutic effect without repeated dosing.

“This is an exciting time for immunotherapy as we transfer knowledge from the lab to clinic. There’s a renewed enthusiasm to manipulate the immune system therapeutically A– from vaccines and antibodies to combining these modalities and improving response rates.”

The findings will be presented at ASCO by Timothy J. Vreeland, M.D., resident at Brooke Army Medical Center. The trial is funded in part by Antigen Express, the company that licenses the vaccine technology. Based on this study, Antigen Express plans to apply for a special protocol assessment from the US Food and Drug Administration to continue Phase III research needed on the vaccine.

###

Other researchers contributing to the study include: Diane Hale, M.D., Alan Sears, M.D. G. Travis Clifton, M.D., Nathan Shumway, D.O. and George Peoples, M.D., from Brooke Army Medical Center; Sathibalan Ponniah, Ph.D., from Uniformed Services University of the Health Sciences; and Sonia Perez, Ph.D., Michael Papamichail, M.D., Ph.D. and Alexandros Ardavanis, M.D. from Saint Savas Cancer Hospital, Cancer Immunology and Immunotherapy Center in, Athens, Greece.

Contact: Laura Sussman
mailto:lsussman@mdanderson.org - lsussman@mdanderson.org
713-745-2457
http://www.mdanderson.org/ - University of Texas M. D. Anderson Cancer Center

http://www.breakthroughdigest.com/medical-news/hybrid-vaccine-demonstrates-potential-to-prevent-breast-cancer-recurrence/ - http://www.breakthroughdigest.com/medical-news/hybrid-vaccine-demonstrates-potential-to-prevent-breast-cancer-recurrence/



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 19 2012 at 12:27pm
Established Cancer Vaccine Works Better In Tandem With FDA-Approved Kidney Transplant Drug
A team from the Perelman School of Medicine and the Abramson Family Cancer Research Institute at the University of Pennsylvania found that the FDA-approved drug daclizumab improved the survival of  http://www.medicalnewstoday.com/articles/37136.php - breast cancer  patients taking a  http://www.medicalnewstoday.com/info/cancer-oncology/ - cancer vaccine by 30 percent, compared to those patients not taking daclizumab. This proof-of-concept study is published this week in Science Translational Medicine. Senior authors of the study are Robert H. Vonderheide, MD, DPhil, associate professor of Medicine, and James Riley, PhD, associate professor of Microbiology. 

The team proposed that daclizumab, already used for kidney transplantation, would be effective in depleting regulatory T cells (Tregs) and restoring the immune system's ability to fight tumors. Tregs are an important population of white blood cells that help turn off the immune system when the system's job is done. Cancer immunotherapy has been used for the last decade, but researchers have been trying to tweak the system to get immune cells to react more robustly to destroy tumors. In time, though, the body slams on the breaks, rendering vaccines less effective. 

Tumor cells exploit Tregs, drawing them to the tumor area. Tregs are essentially hijacked by the tumor, surrounding even the smallest tumors in a protective shell, preventing other tumor-fighting white blood cells from getting to tumor cells at the core. 

Tregs rely on a particular protein, called IL-2, for most of their functions. Daclizumab is an antibody that binds to the CD25 receptor on the surface of Tregs to which IL-2 binds. Tregs are deprived of IL-2 in the presence of daclizumab since it binds to the CD25 receptor instead of IL-2. But rather than causing Tregs to die, using normal lymphocytes from a biobank at Penn run by Riley, the team found the lack of IL-2 forces Tregs to convert into normal T cells that no longer surround the tumor. Once this happens, the tumor-fighting immune cells might be able to make their way into the tumor. 

To bring this idea to patients, the team then designed a clinical trial, which was directed by co-author Kevin Fox, MD, professor of Medicine, and administered daclizumab to 10 patients with metastatic breast cancer prior to giving them an experimental breast cancer vaccine developed and manufactured at Penn. 

"Daclizumab worked incredibly well," says Vonderheide. There were no detectible side effects, and the T-cell conversion in the patients on daclizumab lasted two months. Their tumors didn't shrink, but in six out of the 10 patients the tumors did stop growing. And, the daclizumab patients had an increased survival of about seven months compared to patients on the cancer vaccine alone. 

To date, says Vonderheide, all previous attempts to eliminate Tregs have been toxic and short-lived, but the effects of daclizumab were observed to be rapid, prolonged, and consistent. 

"Although we tested our approach in patients with breast cancer, we know that Tregs can block the immune response against most human cancers," says Vonderheide. "Drugs like daclizumab might be useful for most cancer patients, especially those receiving other types of immune therapy. Although Tregs do help prevent autoimmunity, we did not observe an autoimmune response because we did not convert all Tregs in the body, only those cells that seem to protect the tumor. Going after only some, but not all Tregs, we believe, was an important and unique aspect of our study. Although there is a great deal of work to do to confirm our findings, we believe this will have major implications for cancer vaccine regimens in other types of cancer." 

Although daclizumab is not currently available from its manufacturer, a second trial with a related FDA-approved drug is slated to open for enrollment at Penn this summer for patients with metastatic breast cancer. 
http://www.medicalnewstoday.com/releases/245507.php - http://www.medicalnewstoday.com/releases/245507.php



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Sep 25 2012 at 9:21pm
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=125&abstractID=102964 - http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=125&abstractID=102964

-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 09 2012 at 8:30am
U.S. Army surgeons exhibited new research findings in two poster presentations at the American College of Surgeons Clinical Congress. 

The poster presentation titled, "Assessment of Disease Features and Immune Response in Breast Cancer Patients with Recurrence after Receiving AE37, a HER2 Peptide Vaccine," outlined outcomes of injecting AE37, a HER-2 derived vaccine, in  http://www.medicalnewstoday.com/articles/37136.php - breast cancer  survivors following completion of standard therapy. Those who received injections of AE37 were more likely to survive disease-free than the control group. 

Meanwhile, the poster presentation titled, "A NSQIP Evaluation of Practice Patterns and Outcomes Following Surgery for Anorectal Abscess and Fistula in Patients with and without Crohn's Disease," showed patients with Crohn's Disease (CD) - a form of inflammatory bowel disease - had more aggressive anorectal abscess and fistula disease and suffered more complications following emergency surgery than patients who did not have CD. 

AE37 breast cancer vaccine creates robust immunologic response in cancer survivors 

The poster "Assessment of Disease Features and Immune Response in Breast Cancer Patients with Recurrence after Receiving AE37, a HER2 Peptide Vaccine," showed after completing standard treatment, breast cancer survivors who received injections of AE37 with granulocyte-macrophage colony-stimulating factor (GM-CSF) - an immune stimulant - were more likely to survive five years disease-free than a control group that received GM-CSF alone. AE37 works by stimulating the immune system to recognize and target for destruction a protein called HER2 that is expressed at some level by most breast cancer cells. 

While AE37 did not prevent recurrence in all patients, it provoked an immunologic response in patients across the board, including survivors at high risk of recurrence, those with the hard-to-treat "triple negative" form of breast cancer and those with lower levels of HER2 expression. "Patients with a lower level of expressed HER2 protein, who wouldn't be eligible for the HER2-binding antibody, trastuzumab ( http://www.medilexicon.com/drugs/herceptin_485.php - Herceptin ), had a survival rate of more than 88 percent, compared to 70 percent in the control group," said U.S. Army Capt. John Berry, MD, a research associate. "The vaccine may have benefited patients with less aggressive  http://www.medicalnewstoday.com/info/cancer-oncology/ - cancers ." 

Study director Col. George E. Peoples, M.D., explained how the Cancer Vaccine Development Program differs from other groups investigating cancer vaccines. "Our program was one of the first to enroll cancer survivors with healthy immune systems rather than focus on people with end-stage, metastatic cancer. Our goal is to increase health and survivorship in this group, including specifically those with a high risk of cancer recurrence." 

This study is part of an ongoing prospective, multi-center, randomized, single-blinded phase IIb adjuvant therapy trial. AE37 was co-developed by the Cancer Vaccine Development Program, housed at Brooke Army Medical Center in San Antonio, Texas. 

Capt. Diane F. Hale, M.D., Sonia Perez, Ph.D., Capt. Timothy Vreeland, M.D., Capt. Dabney Raetasha, M.D., Michael Papamichail, M.D., Ph.D., Maj. Guy T. Clifton, M.D., Capt. Alan Sears, M.D., Sathibalan Ponniah Ph.D., and Elizabeth A. Mittendorf, M.D., FACS, also participated in the study. 

More complications for Crohn's Disease patients following emergency colorectal surgery 

Also presented today at Clinical Congress, the poster "A NSQIP Evaluation of Practice Patterns and Outcomes Following Surgery for Anorectal Abscess and Fistula in Patients with and without Crohn's Disease," discussed outcomes for CD patients following emergency surgery for anorectal abscess and fistula. 

Lt. Col. Scott R. Steele, M.D., based at Madigan Army Medical Center, presented a retrospective review of medical data from the American College of Surgeons National Surgical Quality Improvement Program database (ACS-NSQIP, 2005-2010) to calculate 30-day outcomes of patients with and without underlying CD. 

"People with Crohn's Disease are known for having a more aggressive form of anorectal disease and this study affirms that," said Steele. "Study results also showed that complications following emergency colorectal procedures were more prominent in patients with CD than patients without the disease." 

The study data included 7,218 patients who met inclusion criteria with a mean age of 45 years. Even though the majority of patients studied were male (64 percent), CD patients presenting with anorectal disease were younger and more frequently female. 

Capt. Marlin Wayne Causey, M.D., Capt. Dan Nelson, D.O., Lt. Col. Eric K. Johnson, M.D., Justin A. Maykel, M.D., Brad Davis, M.D., David E. Rivadeneira, M.D., and Brad Champagne, M.D., also participated in the study. 
http://www.medicalnewstoday.com/releases/251144.php - http://www.medicalnewstoday.com/releases/251144.php


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 30 2012 at 8:27pm

In Mice, Combining Cancer Vaccine and Low-Dose Anti-Angiogenesis Drug Shows Promise against Breast Cancer

A combination of a  http://www.cancer.gov/cancertopics/factsheet/Therapy/cancer-vaccines - therapeutic cancer vaccine  and low doses of a drug that blocks tumor blood vessel growth (an  http://www.cancer.gov/dictionary?CdrID=46739 - angiogenesis inhibitor ) may be an effective treatment for  http://www.cancer.gov/cancertopics/types/breast - breast cancer , according to a study in mice.

In two different mouse models of breast cancer, the combination treatment shrank tumors more than either treatment alone, and in one model it also improved survival.

Dr. Rakesh Jain and his colleagues from Massachusetts General Hospital and Harvard Medical School published the  http://www.ncbi.nlm.nih.gov/pubmed/23045683 - findings  October 8 in the Proceedings of the National Academy of Sciences.

Evidence from both human and animal studies has suggested that lower doses of angiogenesis inhibitors can “normalize” tumor blood vessels, making them less leaky and more functional—an effect that could improve the delivery of other therapies. And several recent studies suggest that abnormal tumor vasculature “fosters an immunosuppressive  http://www.cancer.gov/dictionary?CdrID=561725 - [tumor] microenvironment ” that may help tumors evade detection or attack by the immune system, the researchers wrote. If so, they continued, normalizing the vasculature could improve vaccine efficacy.

They tested low and high doses of the angiogenesis inhibitor DC101 alone or in combination with a therapeutic vaccine in different  http://www.cancer.gov/dictionary?CdrID=561606 - mouse models  of breast cancer. Based on previous research, they explained, “the schedule of combination treatment…was designed to synchronize vascular normalization and  http://www.cancer.gov/dictionary?cdrid=44928 - T-cell  activation [by the vaccine].”

The researchers also looked for clues that could explain why the combination of the vaccine and low-dose angiogenesis inhibitor was more effective. Compared with blood vessels in mice that received higher doses of DC101 and the vaccine, they found that those in mice treated with lower doses of DC101 and the vaccine were more stable and more evenly distributed throughout the tumor. This appeared to increase the infiltration of immune cells into the tumor following vaccination and to encourage a stronger immune response to the tumor.

According to Dr. James Gulley of NCI’s  http://ccr.cancer.gov/ - Center for Cancer Research  (CCR), the study findings are consistent with recent research conducted by Dr. Benedetto Farsaci in CCR’s  http://ccr.cancer.gov/labs/lab.asp?labid=39 - Laboratory of Tumor Immunology and Biology , involving a therapeutic cancer vaccine in combination with  http://www.cancer.gov/cancertopics/druginfo/sunitinibmalate - sunitinib  (Sutent).

Clinical trials to test a therapeutic vaccine with low doses of an angiogenesis inhibitor in women with breast cancer are in the early planning stages, Dr. Jain said.

http://www.cancer.gov/ncicancerbulletin/103012/page3#d - http://www.cancer.gov/ncicancerbulletin/103012/page3#d



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: christina1961
Date Posted: Nov 17 2012 at 1:43pm
http://www.cleveland.com/metro/index.ssf/2012/11/breast_cancer_vaccine_research.html - http://www.cleveland.com/metro/index.ssf/2012/11/breast_cancer_vaccine_research.html

-------------
2.5 cm TNBC, BRCA-, diag. 2/11, neoadj chemotherapy, uni MX, y2cm,2/16 nodes, RCBII, tumor retested 5-10%ER+,PR-,Her2-, rads, clin trial eribulin 10/11-2/12, tamox.


Posted By: Lee21
Date Posted: Dec 01 2012 at 12:44pm

Early efficacy analysis of the AE37 vaccine in patients with HER2 low-expressing and triple-negative breast cancer.


Sub-category:
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_category_abstracts_view&confID=125&subCatID=483 -

Category:
Systemic Therapy

Meeting:
http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_meeting_categories_view&confID=125 -

Session Type and Session Title:
Poster Discussion Session B 
General Poster Session B

Abstract No:
109

Citation:
J Clin Oncol 30, 2012 (suppl 27; abstr 109)

Author(s):
Elizabeth Ann Mittendorf, Sonia A. Perez, Diane F. Hale, Timothy J. Vreeland, Alan K. Sears, Guy T. Clifton, Alexandros Ardavanis, Nathan M. Shumway, James L. Murray, Sathibalan Ponniah, Michael Papamichail, George Earl Peoples


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^) here and in the printed Proceedings.

http://www.asco.org/portal/jsp/ascov2/generateAbstractCOI.jsp?abstractId=102964 - Abstract:

Background: Peptide vaccines comprised of HLA class II epitopes, which elicit CD4+ T cell responses, play a critical role in potentiating immune responses. We are conducting a randomized phase II trial of AE37, a hybrid peptide created by the addition of the Ii-Key moiety (LRMK) to the HER2 helper epitope, AE36 (HER2 aa776-790). Here, we present efficacy data focusing on outcomes in patients with low HER2 (IHC 1+ or 2+) expression and triple negative breast cancer (TNBC). Methods: The trial is enrolling node positive or high risk node negative breast cancer patients with any degree of HER2 expression (IHC 1+, 2+ or 3+ or FISH > 1.2) rendered disease-free following standard of care therapy. Patients are randomized to receive either AE37+GM-CSF or GM-CSF alone in 6 monthly intradermal inoculations followed by booster inoculations administered every 6 months. Results: The trial has enrolled 254 patients; 105 in the vaccine group (VG) and 149 in the control group (CG). After a median follow-up of 22.3 months, the disease-free survival (DFS) rate in the VG is 90.3% vs 81.1% in the CG (p=.46), a 49% risk reduction. Evaluating patients with low HER2 expression (IHC 1+ or 2+), there are 53 VG patients and 77 CG patients. The groups are well-matched with respect to the percentage of patients with high grade tumors, tumors > 2cm, the rate of node positivity and ER/PR status (all p>.5). The DFS rate in the VG of low HER2 expressers is 89.8% vs 68.2% in the CG (p=.12), a 68% risk reduction. When limiting analyses to patients with TNBC (ER/PR negative, HER2 1+ or 2+), there are 13 VG patients and 23 CG patients. The groups are again well-matched with the exception of control patients having a larger percentage of tumors > 2 cm (70% vs 31%; p=.02). The DFS rate in the VG of TNBC patients is 83.3% vs 47.6% in the CG (p=.23), a 68% risk reductionConclusions: Early analyses suggest clinical benefit to vaccination with AE37, particularly in patients with low HER2-expressing tumors. Importantly, the benefit appears to persist in TNBC patients. Patients will continue to be followed per protocol for 5 years; however, these data suggest that a subsequent phase III trial should evaluate the vaccine in patients with low HER2-expressing disease to include TNBC.


Presented at the 2012 ASCO Breast Cancer Symposium.  A phase 3 trial is supposed to be in the works.



-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Dec 01 2012 at 12:50pm
Lee,

Thanks for posting this information.  "The DFS rate in the VG of TNBC patients is 83.3% vs 47.6% in the CG (p=.23), a 68% risk reduction."  Promising indeed.  Hope they move to Phase III trials very soon or we see this become available adjuvant therapy for all TNBC.  I'd take a 68% risk reduction any day.

Donna


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Jan 08 2013 at 7:30pm

Emerging Vaccines Take Aim at Preventing Recurrent Breast Cancer

By Joe Munch

Graphic: Disease-free survival
Kaplan-Meier plots depict disease-free survival for patients in the phase I and II trials of the E75 vaccine. Following standard treatment for breast cancer, patients were vaccinated with E75 and granulocyte-macrophage colony-stimulating factor or remained unvaccinated (controls).

Myriad advances have been made in the treatment of breast cancer, and cures are achieved in many patients. However, there are still patients whose cancer recurs, and most of these patients will die of their disease. This indicates a need for other therapies that can be used to prevent recurrent disease. One potential option is breast cancer vaccines. 

“Breast tumors are made up of so many different types of cells that we have to use many different drugs and therapies to treat them,” said Jennifer Litton, M.D., an assistant professor in the Department of Breast Medical Oncology at The University of Texas MD Anderson Cancer Center. “Vaccines come at the cancer in a totally different way than our current systemic therapies do.” Vaccines thus may augment the effects of adjuvant treatments currently used to forestall recurrence. 

Potential clinical role

Several types of adjuvant therapy are used to prevent breast cancer from returning; the therapy or combination of therapies used depends on the individual patients and their disease. For example, radiation therapy is used for patients who have undergone breast-conserving surgery, and chemotherapy may benefit patients at high risk of recurrence. Hormonal therapy with tamoxifen or an aromatase inhibitor is used in patients with estrogen receptor–positive disease, and immunotherapy with trastuzumab is used in those with tumors that highly express human epidermal growth factor receptor 2 (HER2). 

Today, several clinical trials are evaluating the use of breast cancer vaccines—not as an alternative to currently available preventive therapies for recurrent disease but as an additional adjuvant therapy. 

“This is a novel approach specifically for people who want another form of therapy to decrease the chance of the cancer coming back,” Dr. Litton said. “People are looking for something extra that may improve their outcome but doesn’t expose them to a lot of extra toxicity.” 

Peptide vaccines

Cancer vaccines stimulate patients’ immune systems to recognize and kill tumor cells. The vaccines consist of a tumor-associated antigen that, once introduced into a patient’s body, elicits an immune response. Several systems have been devised to deliver tumor-associated antigens into the body, including whole-cell vaccines, viral vector vaccines, and dendritic cell vaccines, which are custom made from the patient’s own white blood cells. The only therapeutic cancer vaccine currently approved by the U.S. Food and Drug Administration is sipuleucel-T (Provenge), a dendritic cell vaccine used in men with metastatic hormone-refractory prostate cancer. 

The breast cancer vaccines being investigated at MD Anderson are of a fourth type, peptide vaccines. Peptide vaccines are made by taking a small amino acid sequence (peptide) from a tumor-associated antigen. The tumor-associated antigen most frequently used in breast cancer vaccines is the HER2 oncoprotein, which promotes tumor growth. 

Once taken from the antigen, the peptide is mixed with an immunoadjuvant to help stimulate an immune response. The immunoadjuvant used in the trials being conducted at MD Anderson is granulocyte-macrophage colony-stimulating factor (GM-CSF), which has been used primarily to treat neutropenia in transplant recipients. 

When the peptide–GM-CSF combination is injected, GM-CSF stimulates the dendritic cells in the area of injection to take up and process the peptide so that it can be better presented to the immune system. The length of the peptide dictates the type of immune cell it stimulates. 

Current clinical studies

Several HER2-derived peptide vaccines are being studied in clinical trials at MD Anderson. Although the vaccines are based on a HER2 peptide, they have the most benefit in the 60% of breast cancer patients with low HER2 expression (1+ or 2+ by immunohistochemistry). 

Phase III trial of E75 

The E75 vaccine (NeuVax) is the most studied of the HER2-derived peptide vaccines. The 9-amino-acid peptide E75 binds with major histocompatibility complex (MHC) class I molecules to stimulate CD8-positive T cells; when these T cells recognize a target as foreign, they attack it and release cytotoxic enzymes to kill it. Because E75 is an MHC class I peptide, the vaccine works only in patients whose cells are positive for human leukocyte antigen (HLA)-A2 or HLA-A3; only cells with those HLA types will present the peptide on the cell surface to activate T cells. 

In May 2012, Elizabeth Mittendorf, M.D., Ph.D., an assistant professor in the Department of Surgical Oncology, and her colleagues published the 24-month landmark analysis of their phase I and II trials of E75. The group’s findings opened the door to the phase III PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) study, currently the only phase III trial of a breast cancer vaccine. Dr. Mittendorf is the overall principal investigator of the multinational study. 

This randomized, double-blind, placebo-controlled trial will enroll approximately 700 breast cancer patients who were rendered disease free following standard treatment. Patients must be positive for HLA-A2 or HLA-A3 and have had cancers that were scored as HER2 1+ or 2+ by immunohistochemistry. The vaccine will be given once a month for 6 months and then given as a booster inoculation every 6 months thereafter through 3 years. Because GM-CSF causes inflammation at the injection site, it will be given to patients in each study group, serving as the immunoadjuvant for the vaccine group and as an active placebo for the control group. The primary endpoint of the study is 3-year disease-free survival. 

Positive results from this trial, researchers hope, would eventually lead to indications for the E75 vaccine in the routine care of breast cancer patients. “We are all cautiously optimistic—and excited—as we wait for the results. If they do show that E75 has significant benefit, it could be an amazing opportunity for our cancer patients,” Dr. Litton said. 

Phase II trial of GP2 and AE37 


The GP2 vaccine works in much the same way as the E75 vaccine. Like E75, the GP2 peptide is 9 amino acids long and binds to MHC class I molecules to stimulate CD8-positive T cells; thus, the vaccine works only in patients who are positive for HLA-A2 or HLA-A3. In contrast, the AE37 peptide, which is longer than the E75 and GP2 peptides, binds to MHC class II molecules and stimulates CD4-positive T cells, thereby eliciting a more robust immune response. Although MHC class II peptides can be HLA-restricted, AE37 is a promiscuous peptide, meaning that blood cells of almost any HLA type can present it. In addition, the AE37 peptide is paired with the Ii-Key protein, which enhances the presentation of the peptide to the immune system. 

Both the GP2 and AE37 vaccines are being investigated in an ongoing phase II trial to determine whether the individual vaccines can prevent the recurrence of node-positive or high-risk node-negative breast cancer. Patients are sorted into groups depending on their HLA status and then randomly assigned to receive the appropriate vaccine plus GM-CSF or GM-CSF alone (as the control). 

The AE37 trial’s planned interim analysis revealed that at a median of 22 months, the recurrence rate in the vaccinated patients was 10.3%, whereas the recurrence rate in the control group receiving only GM-CSF was 18.0%. The difference represents a 43% reduction in recurrence rate. 

“These data are encouraging,” Dr. Mittendorf said. “Obviously, we need longer follow-up, and we need to finish accrual in the trial, but the data suggest that it is reasonable to look forward to investigating the AE37 vaccine in a phase III setting.” 

The interim results for the GP2 vaccine are not yet available. 

Potential benefits 

One of the benefits of peptide vaccines such as those being investigated at MD Anderson is that they can be given “off the shelf.” This makes them more convenient and less expensive than the custom-made dendritic cell vaccines. 

Dr. Litton, who has referred a number of patients to the breast cancer vaccine trials, said that patients’ enthusiasm about participating in a vaccine trial has been overwhelmingly positive. “Some patients tell me that they feel empowered by using their own bodies, their own immune systems, to fight the cancer,” she said. 

But the main reason the trials are so popular with patients is that the vaccines offer a potential anticancer benefit with very little risk of toxicity. Most patients have a grade 1 or 2 local toxic response, which means redness at the injection site; and some patients experience grade 1 or 2 systemic symptoms, mostly in the form of minor flu-like symptoms for 4–6 hours after receiving the vaccine. 

“These are people who have gone through chemotherapy, lost their hair, and had terrible gastrointestinal side effects, toxicity in their nails, and all those other things,” Dr. Mittendorf said. “So a treatment that is basically not toxic is very attractive.” 

Dr. Litton echoed Dr. Mittendorf’s sentiments. “It has not been a hard trial for people to become interested in. In fact, I’ve had several people come from different parts of the country just to be part of the trial,” Dr. Litton said. “And we really appreciate all the patients who have stepped forward to participate. It’s always important to encourage people to participate in clinical trials; otherwise we could never move forward with therapies such as this.” 

These vaccines are not for everyone, however. Earlier clinical trials revealed that the peptide vaccines had limited efficacy in patients with late-stage, metastatic breast cancer. 

“There’s a long list of reasons why these vaccines are not set up to be administered to patients who have diffusely metastatic disease,” Dr. Mittendorf said. “It would be difficult, with a peptide vaccine, to mount enough of an immune response to eradicate bulky disease. The microenvironment and immune environment around tumors change as tumors progress, so bulky metastatic tumors also have a less favorable environment for the immune system to function in. And a lot of patients with diffusely metastatic disease have received multiple lines of chemotherapy, which we suspect has a detrimental effect on the immune system.” 

Future directions 

The future of breast cancer vaccines holds many possibilities. Antigens such as cyclin E and folate-binding protein may be targeted for vaccination. Novel immunoadjuvants are being developed that may elicit an immune response more potent than that elicited by GM-CSF. And new approaches using vaccines and harnessing other aspects of the body’s immune system against recurrent breast cancer may be forthcoming. 

“I would like to see some of these vaccines combined with other exciting immunotherapies that are coming on board,” Dr. Mittendorf said. For instance, a vaccine could be paired with a drug that inhibits CTLA-4, a protein that downregulates T cells. “Ipilimumab, an antibody that targets CTLA-4, could be used to take the brakes off the immune system. A vaccine would stimulate the T cells, and the anti–CTLA-4 treatment would allow them to proliferate,” she said. 

Eventually, such vaccines could be used to treat patients much earlier in the course of their disease. “I think it would be an exciting route to look forward to in the frontline setting as well,” Dr. Litton said. “We could potentially cure more people up front at the time of diagnosis.”

FURTHER READING

Mittendorf EA, Alatrash G, Xiao H, et al. Breast cancer vaccines: ongoing National Cancer Institute–registered clinical trials. Expert Rev Vaccines 2011;10:755–774.

For more information, call Dr. Elizabeth Mittendorf at 713-792-2362 or Dr. Jennifer Litton at 713-792-2817.

http://www2.mdanderson.org/depts/oncolog/articles/13/1-jan/1-13-1.html - http://www2.mdanderson.org/depts/oncolog/articles/13/1-jan/1-13-1.html



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: Lee21
Date Posted: May 24 2013 at 2:46pm
Update on AE37 vaccine:
http://www.dailymarkets.com/stock/2013/05/22/generex-announces-asco-presentations-on-the-antigen-express-advanced-stage-ae37-cancer-vaccine/" rel="nofollow - http://www.dailymarkets.com/stock/2013/05/22/generex-announces-asco-presentations-on-the-antigen-express-advanced-stage-ae37-cancer-vaccine/

Reminder: ASCO annual meeting May 31-June 4, 2013.
Link to abstracts:
http://chicago2013.asco.org/abstracts" rel="nofollow - http://chicago2013.asco.org/abstracts


-------------
12/9/11 @59,IDC,grade3, TNBC,3cm(MRI),SLNB0,stage IIA, BRCA1 variant
1/30/12 DD AC-T, 6/7/12 Lumpectomy, ypT1b(0.8 cm), 7/9/12 Rads x 30
11/9/12, clinical trial cisplatin/rucaparib, cisplatin-only arm


Posted By: 123Donna
Date Posted: Jul 13 2013 at 12:24pm
Why cancer vaccines haven't worked

A vaccine that launches an immune attack on cancer cells has so far proved to be better in theory than in practice, and researchers may finally understand why.

http://faculty.mdanderson.org/Willem_Overwijk/" rel="nofollow - Willem Overwijk, Ph.D. , associate professor in MD Anderson’s Department of Melanoma Medical Oncology, and his colleagues found that a mineral oil known as incomplete Freund’s adjuvant (IFA), added to cancer vaccines to stimulate the immune system, might do too good a job.

The  http://www.mdanderson.org/publications/annual-report/issues/2011-2012/vaccines-hold-promise.html" rel="nofollow - vaccine  effectively activates T cells, which are supposed to target cancer cells and destroy them — shrinking tumors and preventing them from spreading to other locations and seeding new growths. But because IFA is not biodegradable, it remains under the skin at the injection site, acting as an irresistible bait for the T cells.

“Vaccines stimulate production of T cells primed to attack the target cancer, and there are many T cells in the bloodstream after vaccination. We found that only a few get to the tumor while many more are stuck at, or double back to, the vaccination site,” Overwijk says.

Essentially, he says, the vaccine competes with the tumor for the attention of the immune cells. The vaccine, because of its powerful ability to stimulate the defensive cells, tends to be more dominant. “That explains why we find nice levels of T cells in blood after vaccination but no correlation with a response against tumors in patients,” Overwijk says.

Engineering flaw discovered 

The oil may not be the only saboteur. It’s also possible that the tumor itself sends out inhibitory factors that either disguise the tumor from immune sentries, or discourage T cells from venturing too close. But if oil is part of the problem, then switching to a less persistent formulation may improve responses to cancer vaccines.

Meanwhile, Overwijk and his colleagues infer that a possible solution would be to reduce the size and persistence of vaccine “depots” at the injection site. They’ve tested a vaccine based on a biodegradable saline solution instead of IFA, and found antigens cleared more quickly but did not spark the desired T cell response. Adding co-stimulating agents to the saline vaccine corrected this effect, allowing more T cells to attack the tumor and leaving few at the injection site.

“It’s an engineering flaw in those vaccines that we didn’t appreciate until now,” Overwijk says. “Fortunately, our results also directly instruct us how to design new, more powerful vaccine formulas for treating people with cancer.”

Reported in the March 3, 2013, online edition of Nature Medicine


http://www.mdanderson.org/publications/conquest/issues/2013-summer/cancer-vaccines.html" rel="nofollow - http://www.mdanderson.org/publications/conquest/issues/2013-summer/cancer-vaccines.html


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 27 2013 at 7:10pm
http://www.gloucestertimes.com/cnhinewsservice-all/x1253330526/Why-arent-there-more-cancer-vaccines" rel="nofollow - Why aren't there more cancer vaccines?

http://www.gloucestertimes.com/cnhinewsservice-all/x1253330526/Why-arent-there-more-cancer-vaccines/?state=taberU" rel="nofollow - http://www.gloucestertimes.com/cnhinewsservice-all/x1253330526/Why-arent-there-more-cancer-vaccines/?state=taberU




-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Feb 13 2014 at 11:17pm
A VACCINE that can prevent breast cancer returning has been developed by Australian scientists and could be on the market within five to ten years.

http://www.news.com.au/lifestyle/health/breast-cancer-vaccine-developed-by-australian-scientists-can-stop-disease-returning/story-fneuz9ev-1226826564070" rel="nofollow - http://www.news.com.au/lifestyle/health/breast-cancer-vaccine-developed-by-australian-scientists-can-stop-disease-returning/story-fneuz9ev-1226826564070

http://www.ascendbiopharma.com/philosophy/asn-004/" rel="nofollow - http://www.ascendbiopharma.com/philosophy/asn-004/


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: sabinecalifornia
Date Posted: Feb 14 2014 at 9:51am
I wish it would be available sooner.

Sabine

-------------
DX TNBC 7/11 @ age 50, Stage 2A Grade 3, 1/19, LE/AD 8/11, BRCA1/2 neg.,
4 A/C, 10 Taxol, 2 Abraxane due to allerg. react. to Taxol, fin 3/12. 33 Rads 6/12. NED CT 8/12, 10/13, 10/14


Posted By: 123Donna
Date Posted: Apr 28 2014 at 8:51pm
Update on the E75 (NeuVax) Vaccine:

USU-HJF EFFORT TO LICENSE PROMISING BREAST CANCER VACCINE WINS AWARD

http://www.freshnews.com/news/931369/usu-hjf-effort-license-promising-breast-cancer-vaccine-wins-award" rel="nofollow - http://www.freshnews.com/news/931369/usu-hjf-effort-license-promising-breast-cancer-vaccine-wins-award

Clinical Trials:

http://clinicaltrials.gov/ct2/results?term=NeuVax+and+breast+cancer&Search=Search" rel="nofollow - http://clinicaltrials.gov/ct2/results?term=NeuVax+and+breast+cancer&Search=Search


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Apr 30 2014 at 8:26am
We'll have to keep an eye on this research and Phase 1 Clinical Trials.

Promising new approach targets cancer protein to slow tumor growth

Sometimes a full-on assault isn't the best approach when dealing with a powerful enemy. A more effective approach, in the long run, may be to target the support system replenishing the supplies that keep your foe strong and ready for battle.

A group of researchers from the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania is pursuing this strategy by employing a novel DNA vaccine to kill  http://www.medicalnewstoday.com/info/cancer-oncology/" rel="nofollow - cancer , not by attacking  http://www.medicalnewstoday.com/articles/249141.php" rel="nofollow - tumor  cells, but targeting the blood vessels that keep them alive. The vaccine also indirectly creates an immune response to the tumor itself, amplifying the attack by a phenomenon called epitope spreading. The results of the study were published this month in the Journal of Clinical Investigation.

Previous studies have targeted tumor angiogenesis (the formation of new blood vessels that feed the tumor cells). However, this approach can also interfere with normal processes involved in wound healing and development. Penn researchers avoided this pitfall by designing a DNA vaccine that specifically targets TEM1 (tumor endothelial marker 1), a protein that is overexpressed in tumors and poorly expressed in normal tissues.

"We demonstrated that by targeting TEM1, our vaccine can decrease tumor vascularization, increase hypoxia of the tumor and reduce tumor growth," says Andrea Facciabene, PhD, research assistant professor of Obstetrics and Gynecology and a faculty member in the Ovarian Cancer Research Center at Penn Medicine. "Our results confirm that we were directly targeting the tumor vasculature and also indirectly killing tumor cells through epitope spreading."

The Penn team injected mice with a DNA fusion vaccine called TEM1-TT, created by fusing TEM1 complementary DNA with a fragment of the  http://www.medicalnewstoday.com/articles/163063.php" rel="nofollow - tetanus  toxoid (TT). In mouse models of three cancer types (breast, colon, and cervical), tumor formation was delayed or prevented in mice vaccinated with the TEM1-TT DNA vaccine. Specifically, they found that the mouse tumors had suppressed growth, decreased tumor vessel formation, and increased infiltration of immune cells into tumors.

The researchers found that the DNA vaccine, after killing the endothelial cells that make up the tumor vessels (vasculature), also resulted in epitope spreading, meaning that the immune cells of the mice gathered pieces of dead tumor cells (due to hypoxia) to create a secondary immune response against the tumor itself. The vaccine induced specific T cells to fight other tumor cells expression other proteins, in addition to TEM1, thus increasing its therapeutic efficacy.

The new DNA vaccine approach to fight cancer is showing great potential compared to previous studies that focused on tumor cells rather than the blood vessels that allow tumor cells to thrive.

"Until now there have been a lot of clinical trials using DNA vaccines to target tumors themselves, but unfortunately the results have been disappointing," Facciabene notes. "This is a different approach which should heighten optimism for cancer vaccines in general. Moreover, based on what we've seen in our mouse studies, this vaccine doesn't seem to show any significant side effects."

The prevalence of TEM1 in a wide range of tumor types coupled with its scarcity in normal vessels makes it a suitable target both for a prophylactic defense against cancer and a complement to other therapies such as radiotherapy and  http://www.medicalnewstoday.com/articles/158401.php" rel="nofollow - chemotherapy . "Using this vaccine simultaneously with radiation may eventually have a double synergy," Facciabene says. "Both treatments affect the tumor endothelium, radiotherapy could help the phenomenon of epitope spreading induced by the TEM1-TT vaccine." In addition to ongoing pre-clinical work with human TEM1, Facciabene and colleagues are planning to move on to Phase I human clinical trials.

The authors suggest that TEM1 may also be an excellent target as a prophylactic cancer vaccine for individuals that have a high risk of developing  http://www.medicalnewstoday.com/articles/159675.php" rel="nofollow - ovarian cancer , such as carriers of the BRCA1/2 mutations, predominant in breast and ovarian cancer. Research to develop those types of strategies is a key goal of Penn's Basser Research Center for BRCA. As a bonafide vaccine, TEM-TT DNA vaccine generates a memory immune response, which Facciabene says is an ideal attribute for high risk populations.

http://www.medicalnewstoday.com/releases/276019.php?tw" rel="nofollow - http://www.medicalnewstoday.com/releases/276019.php?tw



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 07 2014 at 11:18pm
First Breast Cancer Vaccine Passes Phase 1 Clinical Trials

Doctors at the University of Arkansas for Medical Sciences (UAMS) are done with a Phase I breast cancer vaccine trial.

The breast cancer vaccine induced antibody responses in the “small group of participants who received five injections of the vaccine” in 23 weeks. Consequently, clinical vaccine collaborators Dr .Thomas Kieber-Emmons, PhD, and Dr. Laura Hutchins, M.D., are happy with the trial’s success. Hutchins selected participants for the Phase I trial. Kieber-Emmons developed the vaccine at UAMS.

The trial at UAMS is the first time a breast cancer vaccine has been tested in humans outside of US military families. The human trial trumps research by others—from  http://news.yahoo.com/the-breast-cancer-shot--cleveland-doctor-develops-a-vaccine-113000843.html" rel="nofollow - Dr. Vincent Tuohy  in Cleveland to the United States Army. In October 2013, Tuohy found breast cancer vaccine success in lab mice. Tuohy needed funding for a Phase I trial. UAMS received its funding from a Clinical Translational Award from the Department of Defense Breast Cancer Program.

In 2012, the United States Army’s Cancer Vaccine Development Program was set to begin Phase III trials in the beginning of 2013. You can read more about its program  http://www.army.mil/article/89790/Army_breast_cancer_vaccine_research_achieves_multiple_milestones/" rel="nofollow - here .

Kieber-Emmons’ peptide vaccine was designed to “trigger an immune response that destroys the cancer cells. The peptide (a computer generated chemical compound) “mimics carbohydrates that are attached to the cancer cells and tricks the immune system into attacking those carbohydrates” (UAMS).

Phase II of the trial begins in “the next few months to examine if the vaccine improves the efficacy of preoperative chemotherapy” ( http://www.uamshealth.com/news/?id=5350&sid=1&nid=10111&cid=5" rel="nofollow - UAMS ). In other words, Phase II seeks to determine whether or not the “combination of vaccine and standard chemotherapy improves the benefit from preoperative therapy.”

http://www.vaccinews.net/2014/05/first-breast-cancer-vaccine-passes-phase-i-clinical-trials/" rel="nofollow - http://www.vaccinews.net/2014/05/first-breast-cancer-vaccine-passes-phase-i-clinical-trials/



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: May 14 2014 at 9:01pm
Not breast cancer, but interesting

Mayo Clinic trial: Massive blast of measles vaccine wipes out cancer

http://www.startribune.com/lifestyle/health/259155541.html" rel="nofollow - http://www.startribune.com/lifestyle/health/259155541.html


-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Oct 08 2014 at 10:50pm
http://www.yourhoustonnews.com/health/news/immunotherapy-vaccine-shows-promise-in-preventing-recurrence/article_d973d10f-6187-551b-ac78-a1d056a29662.html?mode=story" rel="nofollow - Immunotherapy vaccine shows promise in preventing recurrence

A new breast cancer vaccine candidate, GP2, provides further evidence of the potential of immunotherapy in preventing disease recurrence.

This is especially the case for high-risk patients when it is combined with a powerful immunotherapy drug. These findings are being presented by The University of Texas MD Anderson Cancer Center at the 2014 American Society of Clinical Oncology’s Breast Cancer Symposium in San Francisco.

“This is an important and different avenue in immunotherapy research, in that we are investigating ways to prevent cancer recurrence by stimulating the immune system to treat cancer,” says principal investigator Elizabeth Mittendorf, M.D., Ph.D., associate professor of Surgical Oncology. “The ultimate goal is to develop a preventative tool that will minimize the risk of recurrence in women who have already had breast cancer and for whom standard therapies have failed.”

One of only a few vaccines of its kind in development, GP2 has been shown to be safe and effective for breast cancer patients, reducing recurrence rates by 57 percent. Further, women with the highest overexpression of HER2, also known as HER2 +3, had no cancer recurrences when they were administered the vaccine after completing trastuzumab (Herceptin), a type of immunotherapy drug known as a monoclonal antibody. HER2 is an oncoprotein that promotes tumor growth and is expressed to some extent in 75-80 percent of breast cancers.

The findings are the result of a phase II randomized trial that paired the GP2 vaccine, designed to stimulate the CD8+ cells, commonly known as “killer” or “toxic” T cells, with an immune stimulant known as granulocyte/ macrophage colony stimulating factor (GM-CSF). The trial included 190 patients with varying levels of HER2; 89 women received the GP2 vaccine with a GM-CSF adjuvant and a control group of 91 patients received GM-CSF alone. Eight patients experienced early recurrence or developed a second malignancy and did not complete the vaccine trial. The vaccine is injected subcutaneously and the initial series consisted of monthly inoculations for six months, followed by four cycles of booster shots administered every six months thereafter. The patients were monitored for nearly three years.

For all 190 patients, including those who did not complete the trial, the disease-free survival rate was 88 percent among those who received the vaccine and 81 percent in the control group — representing a 37 percent reduction in recurrence. Excluding the patients who did not complete the vaccine series, the results are higher — 94 percent DFS rate versus 85 percent who did not get GP2 — a 57 percent risk reduction.

Women with HER2 +3 who were administered trastuzumab as part of the standard of care prior to receiving the vaccine experienced no cases of cancer recurrence. According to Mittendorf, trastuzumab may act like a primer for the vaccine. Trastuzumab stimulates CD4+ T cells to release substances that fight cancer cells and initiates an antibody response. Thus, it may prepare the immune system, making the vaccine even more effective. MD Anderson is now testing this combination of immunotherapies in other clinical trials.

Personalized Immunotherapy

The GP2 study supports previous MD Anderson research on similar breast cancer vaccines, which showed a significant immune response and improved recurrence rates in triple-negative breast cancer patients. Another candidate, E75, known as NeuVax or nelipepimut-S, showed a 50- percent recurrence decrease in high-risk patients. Currently, NeuVax is being tested internationally in a phase III clinical trial.

“We believe many more patients will benefit in some way from immunotherapy,” says Mittendorf. “The challenge will be identifying the right immunotherapeutic approach for each individual patient. When doctors are able to do that, cancer therapy, and immunotherapy specifically, will follow a more personalized approach.”

Other researchers contributing to the study include: Jennifer Litton, M.D.; James Murray, M.D., MPH; Guy Clifton, M.D. from MD Anderson; John Berry, M.D., Nathan Shumway, M.D., Timothy Vreeland, M.D., George Peoples, M.D., Erika Schneble, M.D., Julia Greene, M.D. and Alfred Trappey, M.D. from Brooke Army Medical Center; Sathibalan Ponniah, Ph.D. from Uniformed Services University of the Health Sciences; Alexandros Ardavanis, M.D., Michael Papamichail, M.D. and Sonia Perez, M.D. from Saint Savvas Cancer Hospital in Athens, G

http://www.yourhoustonnews.com/health/news/immunotherapy-vaccine-shows-promise-in-preventing-recurrence/article_d973d10f-6187-551b-ac78-a1d056a29662.html?mode=story" rel="nofollow - http://www.yourhoustonnews.com/health/news/immunotherapy-vaccine-shows-promise-in-preventing-recurrence/article_d973d10f-6187-551b-ac78-a1d056a29662.html?mode=story



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Dec 01 2014 at 8:16pm
New breast cancer vaccine proves safe in early clinical trial

A breast cancer vaccine developed at  http://medicine.wustl.edu/" rel="nofollow - Washington University School of Medicine  in St. Louis is safe in patients with metastatic breast cancer, results of an early clinical trial indicate. Preliminary evidence also suggests that the vaccine primed the patients’ immune systems to attack tumor cells and helped slow the cancer’s progression.

The study appears Dec. 1 in Clinical Cancer Research.

The new vaccine causes the body’s immune system to home in on a protein called mammaglobin-A, found almost exclusively in breast tissue. The protein’s role in healthy tissue is unclear, but breast tumors express it at abnormally high levels, past research has shown.

“Being able to target mammaglobin is exciting because it is expressed broadly in up to 80 percent of breast cancers, but not at meaningful levels in other tissues,” said breast cancer surgeon and senior author William E. Gillanders, MD, professor of surgery. “In theory, this means we could treat a large number of breast cancer patients with potentially fewer side effects.

“It’s also exciting to see this work progress from identifying the importance of mammaglobin-A, to designing a therapeutic agent, manufacturing it and giving it to patients, all by investigators at Washington University,” he added.

The vaccine primes a type of white blood cell, part of the body’s adaptive immune system, to seek out and destroy cells with the mammaglobin-A protein. In the smaller proportion of breast cancer patients whose tumors do not produce mammaglobin-A, this vaccine would not be effective.

In the new study, 14 patients with metastatic breast cancer that expressed mammaglobin-A were vaccinated. The Phase 1 trial was designed mainly to assess the vaccine’s safety. According to the authors, patients experienced few side effects, reporting eight events classified as mild or moderate, including rash, tenderness at the vaccination site and mild flu-like symptoms. No severe or life-threatening side effects occurred.

Although the trial was designed to test vaccine safety, preliminary evidence indicated the vaccine slowed the cancer’s progression, even in patients who tend to have less potent immune systems because of their advanced disease and exposure to chemotherapy.

“Despite the weakened immune systems in these patients, we did observe a biologic response to the vaccine while analyzing immune cells in their blood samples,” said Gillanders, who treats patients at  http://www.siteman.wustl.edu/" rel="nofollow - Siteman Cancer Center  at Barnes-Jewish Hospital and Washington University. “That’s very encouraging. We also saw preliminary evidence of improved outcome, with modestly longer progression-free survival.”

Of the 14 patients who received the vaccine, about half showed no progression of their cancer one year after receiving the vaccine. In a similar control group of 12 patients who were not vaccinated, about one-fifth showed no cancer progression at the one-year follow-up. Despite the small sample size, this difference is statistically significant.

Based on results of this study, Gillanders and his colleagues are planning a larger clinical trial to test the vaccine in newly diagnosed breast cancer patients, who, in theory, should have more robust immune systems than patients who already have undergone extensive cancer therapy.

“If we give the vaccine to patients at the beginning of treatment, the immune systems should not be compromised like in patients with metastatic disease,” Gillanders said. “We also will be able to do more informative immune monitoring than we did in this preliminary trial. Now that we have good evidence that the vaccine is safe, we think testing it in newly diagnosed patients will give us a better idea of the effectiveness of the therapy.”


http://news.wustl.edu/news/Pages/27732.aspx" rel="nofollow - http://news.wustl.edu/news/Pages/27732.aspx


http://www.foxnews.com/health/2014/12/01/new-breast-cancer-vaccine-proves-safe-in-early-clinical-trial/" rel="nofollow - http://www.foxnews.com/health/2014/12/01/new-breast-cancer-vaccine-proves-safe-in-early-clinical-trial/

http://clincancerres.aacrjournals.org/content/20/23/5964.abstract" rel="nofollow - http://clincancerres.aacrjournals.org/content/20/23/5964.abstract





-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: rosewater
Date Posted: Dec 01 2014 at 9:01pm
Just curious if anyone has taken part in the NeuVax trial?


-------------
DX IDC TNBC 03/14 age 40, Stage 1, Grade 3, 2cm, 0/4Nodes, lumpectomy 04/14, DD A/C x4, Taxol x12, Carboplatin x2, BMX 10/14, rads x28 Finished Jan 14/15, Oopherectomy Jan 29/15 BRCA 2+


Posted By: 123Donna
Date Posted: Dec 04 2014 at 8:10pm
http://www.fredhutch.org/en/news/center-news/2014/12/breast-cancer-vaccine-shows-promise.html" rel="nofollow - http://www.fredhutch.org/en/news/center-news/2014/12/breast-cancer-vaccine-shows-promise.html

-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Apr 01 2015 at 8:32pm
http://www.siteman.wustl.edu/ContentPage.aspx?id=8651" rel="nofollow - http://www.siteman.wustl.edu/ContentPage.aspx?id=8651

-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 11 2015 at 8:11pm
Cancer protein may spark new vaccine for hard to treat form of breast cancer

http://www.medicalnewstoday.com/releases/297989.php?tw" rel="nofollow - http://www.medicalnewstoday.com/releases/297989.php?tw

New cancer marker may be key to tailored chemotherapy treatment in hard to treat breast cancer – Cancer vaccine target?


http://medicalresearch.com/cancer-_-oncology/breast-cancer/new-cancer-marker-may-be-key-to-tailored-chemotherapy-treatment-in-hard-to-treat-breast-cancer-cancer-vaccine-target/16489/" rel="nofollow - http://medicalresearch.com/cancer-_-oncology/breast-cancer/new-cancer-marker-may-be-key-to-tailored-chemotherapy-treatment-in-hard-to-treat-breast-cancer-cancer-vaccine-target/16489/




-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Mar 11 2019 at 9:03pm
Immune-based therapies are becoming a reality for cancer care

To read the full story:
https://outlook.wustl.edu/the-warrior-within" rel="nofollow - https://outlook.wustl.edu/the-warrior-within

. . .Gillanders’ group is testing neoantigen vaccines in patients with triple negative breast cancer, a form that is difficult to treat. They are conducting trials that combine the current standard of care — surgery, radiation and chemotherapy — with a vaccine in the hope of preventing recurrence.

“Finding the right way to combine traditional therapies with immune therapies such as vaccines, that’s where things are moving,” said Gillanders.

Neoantigen cancer vaccines represent a truly personalized treatment approach; neoantigens vary from patient to patient and from tumor to tumor, so each patient’s vaccine must be made from scratch. That can present challenges with production.

"There aren’t many places that can generate these products under the kinds of conditions that you need to make a vaccine,” said Schreiber.

Fortunately, the School of Medicine and Siteman Cancer Center are home to a Good Manufacturing Practice (GMP) lab, where immunotherapies such as cancer vaccines can be made and tested in clinical trials. Such facilities, which meet exceedingly high standards for consistency and quality, are not typical in most academic medical centers and help keep costs down when producing such expensive individualized treatments. . .




-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15



Posted By: 123Donna
Date Posted: Aug 05 2019 at 10:14am
Anixa Biosciences, Cleveland Clinic enter license agreement for breast cancer vaccine technology

San Jose, Calif.-based biotechnology company https://www.anixa.com/" rel="nofollow - Anixa Biosciences Inc. (Nasdaq: ANIX) announced Wednesday, July 17, that it has established a strategic alliance and license agreement with https://my.clevelandclinic.org/" rel="nofollow - Cleveland Clinic for a breast cancer vaccine technology.

Anixa focuses on harnessing the body's immune system to fight cancer.

Cleveland Clinic researcher Dr. Vincent Tuohy has been developing a method to vaccinate women against contracting breast cancer, focused specifically on the most lethal form of the disease: triple negative breast cancer (TNBC). Tuohy has identified a protein that's "retired" from service after a woman has given birth but reappears in many forms of breast cancer, especially TNBC, according to https://ir.anixa.com/press-releases/detail/921/anixa-biosciences-announces-a-strategic-alliance-and" rel="nofollow - a news release .

Vaccinating against this problem, studies have shown, prevents breast cancer in mice. Anixa will work with Tuohy and a Cleveland Clinic team to advance the vaccine to clinical trials in humans to verify the animal studies, according to the release.

"The field of cancer therapy has focused on treating patients after they have contracted cancer," Tuohy said in a prepared statement. "If we could vaccinate patients and never allow the cancer to develop, the impact would be immense for patients and our health care system. Over the last decade we have gained significant understanding about the immune system to contemplate developing cancer vaccines like this."

Tuohy and Cleveland Clinic received a $6.2 million grant from the U.S. Department of Defense in November 2017 to fund the completion of pre-clinical studies as well as the completion of two Phase 1 clinical studies to test the vaccine in patients, according to the release.

"Dr. Tuohy has been working on this technology and pioneering the concept of prevention for over a decade, and has demonstrated the ability to eliminate breast cancer completely in animal studies," said Dr. Amit Kumar, president and CEO of Anixa, in a prepared statement. "We are now ready to work with him and the U.S. DOD to evaluate if similar results are seen in humans. Imagine a world where we would immunize women against breast cancer, similar to the way we have immunized humanity against polio, small pox and other infectious diseases."

https://www.crainscleveland.com/health-care/anixa-biosciences-cleveland-clinic-enter-license-agreement-breast-cancer-vaccine" rel="nofollow - https://www.crainscleveland.com/health-care/anixa-biosciences-cleveland-clinic-enter-license-agreement-breast-cancer-vaccine



-------------
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15




Print Page | Close Window

Forum Software by Web Wiz Forums® version 12.01 - http://www.webwizforums.com
Copyright ©2001-2018 Web Wiz Ltd. - https://www.webwiz.net