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    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 Anixa Biosciences Inc. (Nasdaq: ANIX) announced Wednesday, July 17, that it has established a strategic alliance and license agreement with 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 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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 11 2019 at 9:03pm
Immune-based therapies are becoming a reality for cancer care

To read the full story:

. . .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. . .


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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Aug 11 2015 at 8:11pm
Cancer protein may spark new vaccine for hard to treat form of breast cancer


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




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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Apr 01 2015 at 8:32pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 04 2014 at 8:10pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote rosewater Quote  Post ReplyReply Direct Link To This Post Posted: Dec 01 2014 at 9:01pm
Just curious if anyone has taken part in the NeuVax trial?
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Post Options Post Options   Thanks (1) Thanks(1)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Dec 01 2014 at 8:16pm
New breast cancer vaccine proves safe in early clinical trial

A breast cancer vaccine developed at 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 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


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



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Post Options Post Options   Thanks (1) Thanks(1)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Oct 08 2014 at 10:50pm
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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 14 2014 at 9:01pm
Not breast cancer, but interesting

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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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 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 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” (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/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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 cancer, not by attacking 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 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 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 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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Apr 28 2014 at 8:51pm
Update on the E75 (NeuVax) Vaccine:

Edited by 123Donna - Apr 30 2014 at 8:22am
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Post Options Post Options   Thanks (0) Thanks(0)   Quote sabinecalifornia Quote  Post ReplyReply Direct Link To This Post Posted: Feb 14 2014 at 9:51am
I wish it would be available sooner.

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Post Options Post Options   Thanks (1) Thanks(1)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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.

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Aug 27 2013 at 7:10pm
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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.

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 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


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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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

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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post 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

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Lee21 Quote  Post ReplyReply Direct Link To This Post 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:
Triple-negative

Category:
Systemic Therapy

Meeting:
2012 Breast Cancer Symposium

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.

Abstract Disclosures

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
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