Novel Gene Therapy for Enhancing Anti-Tumor Immunity.
Annual rept. 1 Jul 96-30 Jun 97,
MARYLAND UNIV BALTIMORE
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The major goal of this project is to constitutively express syngeneic MHC class II molecules I-Ad, the T cell costimulatory molecules B7-l, B7-2 or both on murine mammary carcinoma tumor cell lines 410.4 and 66.1 and investigate their ability to induce anti-tumor immunity in the host. Transfectants of both tumor cell lines expressing I-Ad molecules showed significantly slower growth in naive Balbic mice and formed smaller tumors compared to their wild type counterparts, and in some cases were completely rejected. These transfectants showed unimpaired growth in athymic nude mice. Based on these results, it is suggested that the I-Ad positive tumor cells are able to present tumor antigens to and activate the CD4 T cells resulting in a moderate tumor immunity in the naive immunocompetant host. Administration of murine recombinant IL- 12 while reduced the growth of wild type tumor cells, completely abolished the growth of B7-1 transfectants and prevented metastasis. Multiple injections of irradiated I-Ad positive tumor cells induced protective immunity indicating the possible combination of direct and indirect cross priming antigen presentation to the tumor-specific T cells. Using the transfectants coexpressing both I-Ad and B7-1 molecules, the therapeutic value of gene-modified tumor cell vaccine will be investigated.
- Medicine and Medical Research