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Generex Biotechnology, and their wholly owned subsidiary Antigen Express, are developing promising new drugs to treat diabetes, as well as synthetic peptide vaccines targeting HER2/neu cancer and pandemic flu. The flagship product for Generex is Oral-lyn buccal insulin. Antigen Express' leading vaccine is the AE37 HER2/neu synthetic peptide vaccine to prevent breast cancer recurrence. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I am a layman and a shareholder in this company. The left side of Pipeline Review holds blogs regarding Generex and Antigen Express, while the right side offers items of due diligence mixed with my analysis which may be of interest to others seeking to learn about Generex's pipeline. If the left side only shows the latest blog, click on the word home to view them all.

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Wednesday, April 11, 2012

Novel Vaccine Reduces Risk for Breast Cancer Recurrence

The following article was written by Roxanne Nelson and appeared in Medscape on April 11, 2012

An experimental immunotherapeutic vaccine has shown promise in the prevention of disease relapse in high-risk breast cancer patients.

A phase 2 trial, presented here at the American Association for Cancer Research 103rd Annual Meeting, has shown that women who received the AE37 HER2 peptide vaccine developed a specific immune response — an increase in circulating T cells in their blood specific for the HER2 fragment and delayed-type hypersensitivity.

In the study, more patients in the vaccine group (41 of 109 patients) than in the control group (28 of 108 patients) achieved a decrease of more than 90% in T regulatory cells, which can interfere with the immune response.

Immunotherapy is "is a nontoxic and tumor-specific therapy with a long-term memory," said Olivera Finn, PhD, distinguished professor and chair of the Department of Immunology at the University of Pittsburgh in Pennsylvania, who was not involved in the study. "The hope is that once treated it will prevent recurrence."

A number of immunotherapies, including rituximab (Rituxan) and trastuzumab (Herceptin), have already been approved and are being used as first-line treatments, she pointed out.

However, vaccines are generally used to prevent disease, noted Dr. Finn. "To intervene in a therapeutic fashion and to activate the immune system during a disease is a special challenge."

Wider Range Than Trastuzumab

With AE37, "we are aiming to stimulate the host immune system to recognize and kill cancer cells that are expressing the HER2 protein," said study author Diane F. Hale, MD, a research resident in general surgery at the Brooke Army Medical Center at Fort Sam, Houston, Texas.

The vaccine will be used in the adjuvant setting to prevent recurrence, explained Dr. Hale during a press briefing. The vaccine targets HER2, as does trastuzumab, she noted. However, "whereas only about 20% of patients are eligible for [trastuzumab], this vaccine can be used on up to 50% to 60% of patients."

AE37 is the Ii-Key hybrid of the HER2-derived peptide AE36 (776–790). Previously, a phase 1 trial showed that AE37 combined with immunoadjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) demonstrated that the vaccine is safe and able to stimulate CD4+ helper T cells with HER2-specific antitumor activity. Compared with unmodified class II epitopes, the Ii-Key addition, a 4-amino-acid modification, increases vaccine potency.

Immunologic Response Observed

In this prospective, randomized, single-blinded study, Dr. Hale and colleagues compared the AE37 vaccine plus GM-CSF with GM-CSF alone in the prevention of breast cancer recurrence.

The study involved node-positive or high-risk node-negative breast cancer patients; all patients were disease free before entry into the trial, explained Dr. Hale. To date, 217 patients have been enrolled.

The women were randomized to receive AE37 plus GM-CSF or GM-CSF alone in 6 monthly intradermal inoculations. Participants had any level of HER2 expression (immunohistochemistry scores of 1+, 2+, or 3+) and specific immunologic responses to both AE36 and AE37 were evaluated.

The researchers analyzed in vitro responses using the [3H]-thymidine incorporation assay and in vivo responses using delayed-type hypersensitivity reactions. T regulatory cells were measured throughout the vaccination series.

HER2 overexpression was present in 54 patients (49.5%) who received the vaccine and in 51 (47.2%) of the control subjects (P = .783). In the vaccine group, 59 (51.4%) were estrogen-receptor positive, compared with 58 (53.7%) in the control group (P = .985).

"As we would expect, 86% of patients vaccinated with the peptide had a significant delayed-type hypersensitivity response, compared with 27% of those who were not receiving the peptide," said Dr. Hale.

The researchers also evaluated the proliferation response of cells exposed to HER2. "Intuitively, if your immune system is primed to recognize a specific peptide as foreign, it will generate a reaction in vivo and in vitro," she explained. "Patients primed to recognize HER2 as a foreign peptide demonstrated a high response. Conversely, those who did not receive the vaccine had a high nonresponse."

In vitro proliferation responses with a stimulation index of at least 2 were classified as high responders; there were 36 (33.0%) high responders in the vaccine group and 8 (7.4%) in the control group (P < .001). There were 19 (17.4%) low responders (a stimulation index of 1.5 to 2.0) in the vaccine group and 16 (14.8%) in the control group (P = .600). There were 54 (49.5%) nonresponders (a stimulation index below 1.5) in the vaccine group and 84 (77.8%) in the control group (P = .001).

The researchers also looked at T regulatory cells at baseline and after vaccination. "A large number of vaccinated patients had a decrease from baseline, leading us to believe that they had an improved immune response to the vaccine," said Dr. Hale.

Trend Toward Survival Benefit

At a median follow-up of 22 months, 90.1% of patients in the vaccine group had disease-free survival, compared with 82.6% in the control group.

"There was a trend toward survival benefit in the vaccinated patients. On subset analysis of the low-HER2-expression patients, there was an even greater benefit — an approximately 40% reduction of recurrence," said Dr. Hale.

She pointed out that survival statistics are not yet available because it is still too early in the study. The phase 2 study will continue, and there are plans to pursue a phase 3 trial.

The vaccine is being developed by Antigen Express. Eric von Hofe, PhD, president of the company, pointed out that this vaccine is much more cost effective than cellular-based therapies.

"It is meeting an unmet need," he said during the briefing, "and we are bringing it to the adjuvant setting."

American Association for Cancer Research (AACR) 103rd Annual Meeting:
Abstract LB-218. Presented April 3, 2012.

End of article from Medscape.