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Advaxis Live Listeria Vaccine Induces Epitope Spreading.


Newly-Confirmed Activity Strengthens Immune Attack

NORTH BRUNSWICK, N.J. -- Advaxis, Inc. (OTCBB OTCBB

See OTC Bulletin Board (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 microenvironment /mi·cro·en·vi·ron·ment/ (-en-vi´ron-ment) the environment at the microscopic or cellular level.  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 human papilloma virus
n. Abbr. HPV
A DNA virus of the genus Papillomavirus, certain types of which cause cutaneous and genital warts in humans, including condyloma acuminatum.
 (HPV HPV human papillomavirus.

HPV
abbr.
human papilloma virus


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 sexually transmitted disease (STD) or venereal disease, term for infections acquired mainly through sexual contact. Five diseases were traditionally known as venereal diseases: gonorrhea, syphilis, and the less common granuloma inguinale,  in the US and the cause of cervix cancer, 40% of head and neck cancer, as well as penile penile /pe·nile/ (pe´nil) of or pertaining to the penis.

pe·nile
adj.
Of or relating to the penis.



penile

of or pertaining to the penis.
, vulvar vulvar

pertaining to or emanating from the vulva.


vulvar atresia
failure of the orifice to open may occur with imperforate anus as a congenital defect.
 and anal cancer.

Earlier this year, the US Food and Drug Administration (FDA FDA
abbr.
Food and Drug Administration


FDA,
n.pr See Food and Drug Administration.

FDA,
n.pr the abbreviation for the Food and Drug Administration.
) approved Advaxis' application for a Phase II clinical trial Noun 1. phase II clinical trial - a clinical trial on more persons than in phase I; intended to evaluate the efficacy of a treatment for the condition it is intended to treat; possible side effects are monitored
phase II
 in HPV-caused cervical intraepithelial neoplasia cervical in·tra·ep·i·the·li·al neoplasia
n.
Dysplastic changes beginning at the squamocolumnar junction in the uterine cervix that may be precursor to squamous cell carcinoma.
 (CIN CIN cervical intraepithelial neoplasia.
Cervical intraepithelial neoplasia (CIN)
A term used to categorize degrees of dysplasia arising in the epithelium, or outer layer, of the cervix.
), 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 (body, education) University of Pennsylvania - The home of ENIAC and Machiavelli.

http://upenn.edu/.

Address: Philadelphia, PA, USA.
 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 Noun 1. phase I clinical trial - a clinical trial on a few persons to determine the safety of a new drug or invasive medical device; for drugs, dosage or toxicity limits should be obtained
phase I
, 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.
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Publication:Business Wire
Geographic Code:1U2NJ
Date:Oct 8, 2009
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