Company Creates New Form of the Her2 Antigen for Multiple Cancers
NORTH BRUNSWICK, N.J.--(BUSINESS WIRE)-- Scientists at Advaxis, Inc., (OTCBB: ADXS), the live, attenuated Listeria monocytogenes (Listeria) immunotherapy company, recently had their research using ADXS31-164, a live Listeria vaccine that targets Her2, published in a leading peer reviewed journal (Shahabi, et al 2010 Cancer Gene Therapy epublished ahead of print).
Her2 is a tumor antigen found in many cancers including; breast, stomach, brain, and others. The article presents research conducted with this novel active immunotherapy in various Her2 tumor models. The Her2 antigen is the same one targeted by the monoclonal antibody trastuzumab (Herceptin®, Roche Group, OTCQX: RHHBY). Unlike antibodies which can only attack portions of antigens that are outside the cells, cellular immunotherapies like ADXS31-164 can attack the portions of the antigen that protrude inside the cell as well.
Advaxis has begun a manufacturing program for human grade ADXS31-164 for clinical trials.
“Our 2nd generation live Listeria vaccine uses a novel form of the Her2 antigen,” said Advaxis EVP of Science and Operations Dr. John Rothman. “It has performed quite well in a number of preclinical models. We hope to be in the clinic shortly with this agent to develop it for a number of cancer indications.”
About the Research Findings
Advaxis has bioengineered a new chimeric form of the Her2 antigen called chHer2. This chimera is made by isolating the most immunogenic portions of the antigen and reassembling them without the parts of the Her2 molecule that are less immunogenic. Using the company’s proprietary LLO-antigen fusion technology they have bioengineered a second generation live Listeria vaccine to synthesize and secrete LLO-chHer2 (ADXS31-164).
ADXS31-164 was used in a model to assess the effects of the vaccines on the spontaneous (autochthonous) tumor formation in transgenic mice, which are genetically modified to develop Her2 containing tumors spontaneously. The ability of an agent to delay tumor formation and thus “break immune tolerance” in animals born with the oncogene is a difficult test for an immunotherapy. In animals treated with ADXS31-164, 22% never developed tumors over a 1 year observation period, even though they were born with the cancer gene. The authors believe this is the first such report.
Additionally, these authors found effects across the blood brain barrier. When administered intraperitoneally to animals with transplanted Her2 positive brain tumors, ADXS31-164 reduced or eliminated tumors and extended survival.
ADXS31-164 uses the company’s proprietary dal/datA method of attenuation to create a live Listeria vaccine that is both more attenuated (less disease causing) and more immunogenic than prior Listeria vaccine strains. This second generation live Listeria backbone is protected by numerous issued and pending patents. The chimeric antigen chHer2 incorporates 17 known MHC class 1 epitopes, thus providing for many sites of attack along the Her2 antigen. The company is developing this proprietary antigen in vaccines which target Her2 alone, and in the new 3rd generation Listeria vaccines that target two antigens simultaneously. In previously published research (Seavey, et al 2009 Clin Cancer Res; 15(3): 924-32) ADXS31-164 was shown to reduce or eliminate metastases in a transplantable tumor model and significantly extend survival.
About Advaxis, Inc.
Advaxis is a biotechnology company developing proprietary, live, attenuated Listeria monocytogenes (Listeria) vaccines that deliver engineered tumor antigens, which stimulate multiple, simultaneous immunological mechanisms to fight cancer. Today, the Company has nine (9) distinct, cancer-fighting constructs in various stages of development, directly and through strategic collaborations with such recognized sites of excellence as the City of Hope, the Roswell Park Cancer Institute, the National Cancer Institute, the University of Pittsburgh and Cancer Research – UK. Advaxis’ technology was developed by Dr. Yvonne Paterson, professor of microbiology at the University of Pennsylvania and chairperson of Advaxis’ scientific advisory board.
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