Novel Genetherapy for Enhancing Anti-tumor Immunity
Final rept. 1 Jul 94-30 Jun 98
MARYLAND UNIV BALTIMORE
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This report describes the immunogenicity of the transfected tumor cells that co-express I-Ad and B7.1 molecules and this was investigated in different ways. Experiments with both 66.1AdB7 and 410.4AdB7 clones demonstrated that while higher levels of I-Ad expression than B7.1 expression induced tumor rejection in 80 of the mice, in the converse situation the tumors were malignant. The double transfectants expressing higher levels of B7.1 molecules than I-Ad molecules, were clearly able to activate allogenic T cells and were susceptible to lysis by allogenic cytotoxic T cells. Their failure to be rejected by the syngeneic host is not understood. Nonetheless, the transfectants expressing both I-Ad and B7.1 molecules induced a complete abrogation of the lung metastasis compared to the transfectants that express either one of these molecules. It seems unlikely that the failure to reject the potentially immunogenic but malignant transfectants is due to polarization towards the development of Th2 type T cells. Finally, the immunogenic double transfectants by themselves, or with additional help from IL-12 co-administration, are able to significantly reduce metastasis from a previously established wild type tumor. This clearly underscores the therapeutic efficacy of the vaccine tumor cells.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research