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  <1234>
Author
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 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
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 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

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
bak94 View Drop Down
Newbie
Newbie
Avatar

Joined: Oct 23 2011
Status: Offline
Points: 14
Post Options Post Options   Thanks (0) Thanks(0)   Quote bak94 Quote  Post ReplyReply Direct Link To This Post 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!
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 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

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


By 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 guidance, released last year.

The FDA-approved 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 (PGx Reporter 6/2/2010; 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 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
Back to Top
miffyjones View Drop Down
Newbie
Newbie
Avatar

Joined: Dec 11 2011
Location: New Zealand
Status: Offline
Points: 32
Post Options Post Options   Thanks (0) Thanks(0)   Quote miffyjones Quote  Post ReplyReply Direct Link To This Post 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
Lots of Love. MSmile
Back to Top
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13189
Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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 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 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 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

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: Mar 07 2012 at 7:52pm
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
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 07 2012 at 9:35am
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 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
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
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
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 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
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 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
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: 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
123Donna View Drop Down
Senior Member
Senior Member
Avatar

Joined: Aug 24 2009
Location: St. Louis, MO
Status: Offline
Points: 13189
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 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
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 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
 Post Reply Post Reply Page  <1234>
  Share Topic   

Forum Jump Forum Permissions View Drop Down

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