Advaxis Live Listeria Vaccine Induces Epitope Spreading

Newly-Confirmed Activity Strengthens Immune Attack

NORTH BRUNSWICK, N.J.--(BUSINESS WIRE)--Oct 8, 2009 - Advaxis, Inc. (OTCBB: ADXS), the live, attenuated Listeria monocytogenes (Lm) vaccine company, in collaboration with its scientific founder and Scientific Advisory Board Chair Dr. Yvonne Paterson, have shown that epitope spreading occurs in response to a form of the Company's proprietary technology that targets tumor blood vessels (anti angiogenic antigen). Epitope spreading occurs when the immune system is able to attack antigens that are not the original target of an immune therapy but released from tumor cells killed by the therapy. By creating new targets in this way, the immune system can attack more antigens than the one for which the therapy was initially designed; thus, expanding the immune response against a tumor.

This addresses a problem that may occur when tumors mutate away from an immune attack. Escape mutations can develop over time and prevent an immunotherapy from working. Epitope spreading is a mechanism which can provide a continued therapeutic response when escape mutations arise in one or another antigen.

In research published earlier this year (Seavey et al 2009. J. Immunol. 182: 5537–46), and updated last week (Seavey & Paterson, 2009. BCTT. 1:19-30), a live Lm vaccine using the anti-angiogenic target VEGFR2 (Flk-1) fused to the Listeria protein listeriolysin O (LLO) was administered to mice. This vaccine not only attacked its target antigen but induced immune activation against a different tumor antigen Her2/neu, even though the vaccine did not target Her2/neu. Further, this vaccine attacked both tumor blood vessel formation and directly attacked tumor cells that displayed Her2.

“We know that Lm-LLO vaccines do many useful therapeutic things simultaneously; including strong immune activation, therapeutically altering the tumor microenvironment to make it more responsive to immune attack, inducing the synthesis of new immune cells, to name a few,” said Dr. John Rothman, EVP of Science & Operations at Advaxis. “The finding of epitope spreading adds to the growing list of therapeutic mechanisms associated with live Lm therapy.”

About the ADXS11-001 Immunotherapy

ADXS11-001 is a therapeutic vaccine that treats human papilloma virus (HPV) related tumors. Unlike currently marketed prophylactic vaccines that require treatment prior to exposure to the virus, ADXS11-001 treats patients who have already developed cancer as a result of HPV infection. Today, HPV is the most prevalent sexually transmitted disease in the US and the cause of cervix cancer, 40% of head and neck cancer, as well as penile, vulvar and anal cancer.

Earlier this year, the US Food and Drug Administration (FDA) approved Advaxis' application for a Phase II clinical trial in HPV-caused cervical intraepithelial neoplasia (CIN), which is pre-cancerous and a precursor to cervix cancer. For further information on ADXS11-001 please visit: www.advaxis.com/lc.htm.

Advaxis, Incorporated

Based in North Brunswick, New Jersey, Advaxis is developing proprietary Listeria monocytogenes (Lm) cancer vaccines based on technology developed by Dr. Yvonne Paterson, professor of microbiology at the University of Pennsylvania and chairperson of Advaxis' scientific advisory board. Advaxis is developing attenuated live Lm vaccines that deliver engineered tumor antigens, which stimulate multiple simultaneous immunological mechanisms to fight cancer.

In a recent Advaxis Phase I clinical trial, a live Lm vaccine directed against the tumor-associated antigen HPV-16-E7 was safely administered to fifteen (15) women with advanced metastatic cancer of the cervix. Although this first trial of an Lm vaccine in humans was not designed or powered to prove efficacy, Advaxis believes an efficacy signal was observed that will be further explored in two (2) planned Phase II trials in the US and India in cervical cancer and its predecessor condition, cervical intraepithelial neoplasia (CIN). Advaxis now has nine (9) distinct cancer fighting constructs in various stages of development, both directly and with academic collaborators. For further information on the Company, please visit: www.advaxis.com.

Forward-Looking Statements

Certain statements contained in this press release are forward-looking statements that involve risks and uncertainties. The statements contained herein that are not purely historical are forward looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements deal with the Company's current plans, intentions, beliefs and expectations and statements of future economic performance. Forward-looking statements involve known and unknown risks and uncertainties that may cause the Company's actual results in future periods to differ materially from what is currently anticipated. Factors that could cause or contribute to such differences include those discussed from time to time in reports filed by the Company with the Securities and Exchange Commission. The Company cannot guarantee its future results, levels of activity, performance or achievements.

 

 

Contact: Advaxis, Incorporated
Conrad Mir, 732-545-1590
Director, Business Development
Fax: 732-545-1084
conradmir@advaxis.com
www.advaxis.com

 

Posted: October 2009

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