New Posts New Posts RSS Feed - Promising vaccines - Discussion
  FAQ FAQ  Forum Search   Events   Register Register  Login Login

Promising vaccines - Discussion

 Post Reply Post Reply Page  123 4>
Author
christina1961 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Feb 08 2011
Status: Offline
Points: 165
Post Options Post Options   Thanks (0) Thanks(0)   Quote christina1961 Quote  Post ReplyReply Direct Link To This Post Topic: Promising vaccines - Discussion
    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. 
 
 
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.
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13158
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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.  


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

Back to Top
christina1961 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Feb 08 2011
Status: Offline
Points: 165
Post Options Post Options   Thanks (0) Thanks(0)   Quote christina1961 Quote  Post ReplyReply Direct Link To This Post 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.
 
 
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.
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13158
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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/

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

Back to Top
christina1961 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Feb 08 2011
Status: Offline
Points: 165
Post Options Post Options   Thanks (0) Thanks(0)   Quote christina1961 Quote  Post ReplyReply Direct Link To This Post 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

Edited by christina1961 - Jan 30 2012 at 8:47pm
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.
Back to Top
Grateful for today View Drop Down
Senior Member
Senior Member
Avatar

Joined: Sep 21 2011
Location: U.S.A.
Status: Offline
Points: 1835
Post Options Post Options   Thanks (0) Thanks(0)   Quote Grateful for today Quote  Post ReplyReply Direct Link To This Post 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


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://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://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
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
       (started Dec. 2011)
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/

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 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=

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
Back to Top
turtle View Drop Down
Senior Member
Senior Member
Avatar

Joined: Feb 05 2012
Location: Durham, NC
Status: Offline
Points: 161
Post Options Post Options   Thanks (0) Thanks(0)   Quote turtle Quote  Post ReplyReply Direct Link To This Post 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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 15 2012 at 2:38pm
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

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



Edited by Lee21 - Feb 15 2012 at 2:52pm
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
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13158
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Feb 15 2012 at 2:51pm
Lee, 

Is this the trial?


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   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.

ConditionInterventionPhase
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

Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 15 2012 at 5:16pm
Here's the company's NeuVax website
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
Back to Top
ds21 View Drop Down
Groupie
Groupie
Avatar

Joined: Dec 23 2011
Location: Michigan
Status: Offline
Points: 92
Post Options Post Options   Thanks (0) Thanks(0)   Quote ds21 Quote  Post ReplyReply Direct Link To This Post 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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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

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.


Edited by Lee21 - Feb 21 2012 at 8:27pm
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
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13158
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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

Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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. 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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
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
(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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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.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

(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

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


Edited by Lee21 - Mar 01 2012 at 1:46pm
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
Back to Top
turtle View Drop Down
Senior Member
Senior Member
Avatar

Joined: Feb 05 2012
Location: Durham, NC
Status: Offline
Points: 161
Post Options Post Options   Thanks (0) Thanks(0)   Quote turtle Quote  Post ReplyReply Direct Link To This Post 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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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
Trial #
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=%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
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
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

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





Edited by Lee21 - Mar 02 2012 at 9:14am
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
Back to Top
Lee21 View Drop Down
Senior Member
Senior Member
Avatar

Joined: Dec 22 2011
Location: Michigan
Status: Offline
Points: 736
Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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. (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
Back to Top
 Post Reply Post Reply Page  123 4>
  Share Topic   

Forum Jump Forum Permissions View Drop Down

Forum Software by Web Wiz Forums® version 12.01
Copyright ©2001-2018 Web Wiz Ltd.