Novel Gene Therapy for Enhancing Anti-Tumor Immunity
Annual rept. 1 Jul 95-30 Jun 96
MARYLAND UNIV BALTIMORE
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Constitutive expression of the T cell costimulatory molecules B7-l and B7-2 on tumor cells induced antitumor immunity in a variety of tumor models. By contrast, expression of B7-1 or B7-2 on 66.1 and 410.4 mammary carcinoma cell lines resulted in significant delay in their growth, but not complete rejection. However, multiple injections of growth arrested B7-l transfectants induced protective immunity in about 50 of mice. Administration of small amounts of recombinant IL-12 further enhanced the immunogenicity of B7-1 transfectants leading to their rejection, and more importantly prevented metastasis following a subsequent challenge with fairly high dose of wild type tumor cells. These observations indicate that a combination of B7-l and IL-12 was able to mobilize the effector cells resulting in potent antitumor immunity. Further studies are under way to investigate the effect of expression of MHC class II molecules either alone or together with B7- 1 or B7-2 on the induction of antitumor immunity. This will help understand the role of CD4T cells in the development and maintenance of antitumor immunity.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research