VANCOUVER, Sept. 6 /PRNewswire-FirstCall/ - GeneMax Corp. , a biotechnology company specializing in the development of immunotherapeutics for cancer and vaccines for infectious diseases, announced today that a scientific paper co-authored by the Company's Chief Scientific Officer, Dr. Wilfred Jefferies, and his research collaborators from the University of British Columbia and another international institution, has been published in Cancer Research (Sept. 1, 2005 vol. 65 no.17, pages, 7926-7933), the journal of the American Association for Cancer Research. The paper http://cancerres.aacrjournals.org/cgi/content/abstract/65/17/7926 entitled "Restoration of the Expression of Transporters Associated with Antigen Processing in Lung Carcinoma Increases Tumor-Specific Immune Responses and Survival", describes the use of AdhTAP1, an adenovirus containing TAP1 cDNA, to increase the immune response and survival in animal models of lung cancer.
"We have demonstrated that the down-regulation of TAP1 occurs in a wide variety of human lung cancers, and that the corresponding defect in the antigen processing pathway can be reversed using an adenovirus containing TAP1 cDNA," said Dr. Wilfred A. Jefferies. "In an animal model with a lung carcinoma lacking TAP1, the antigen processing was enhanced, leading to tumour specific immune responses and greatly increased animal survival. These data provide critical proof of concept of the type of vectoral systems we plan to take into the clinic."
The investigators assessed human lung cancer biopsy samples (nine small cell and 10 non-small cell carcinomas) for expression of components of the antigen processing pathway (APP) and found only one of the 19 samples expressed normal levels of TAP1. The restoration of TAP1 expression was investigated using a non-replicating adenovirus AdhTAP1 and the mouse lung cancer cell line, CMT.64, which is equivalent to aggressive human carcinomas and has a deficient APP. In ex vivo experiments, AdhTAP1 treatment of CMT.64 resulted in restoration of antigen presentation on the surface of the cancer cells. In addition, AdhTAP1 treatment of dendritic cells (DCs), critical components of the cellular immune response, increased the antigen presenting capabilities of the DCs. Ex vivo treatment resulted in 100% survival of animals receiving the AdhTAP1 modified tumours compared to 100% mortality for the placebo groups. Studies were also conducted in mouse models in which CMT.64 cells were injected into the peritoneal cavity, followed by various treatments. When tumors were treated in vivo with AdhTAP1, also delivered into the peritoneal cavity, mice showed an increased median survival to 68 days, compared to 22 and 25 days for two placebo groups, and showed a 35% cure rate (greater than 100 days), compared to 100% mortality within 48 days in the placebo groups.
Transporters Associated with Antigen Processing (TAP) are ABC transporters responsible for supplying tumor-associated antigens and viral antigens used in the assembly of MHC class I surface molecules. MHC class I molecules are required for the recognition and destruction of tumor cells and virus infected cells by the cellular arm of the immune system. A wide variety of metastatic cancers evade destruction by the immune system due to absent or insufficient amounts of TAP, making the tumors unrecognizable by the immune system.
About GeneMax Corp.
GeneMax Corp. is a biotechnology company specializing in the development of innovative therapeutics and vaccines in the areas of oncology and infectious disease. The companies' lead product, the AdhTAP(OS-1) vaccine enhancer restores and augments antigen presentation and subsequent recognition and killing of cancer cells by the immune system. The company is currently in pre-clinical development in anticipation of a phase I clinical trial.
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