AUGMENTED SYSTEMIC IMMUNITY IN MICE IMPLANTED WITH TUMOR-NECROSIS-FACTOR-ALPHA GENE-TRANSDUCED METH-A CELLS

Syngeneic BALB/c mice bearing methylcholanthrene-induced fibrosarcoma (Meth-A) cells transduced with a tumor necrosis factor (TNF) gene showed a longer life span and tumor regression as compared with mice carrying TNF-non-producing Meth-A cells. To elucidate the mechanism of the reduced tumorigenicity of TNF-producing Meth-A, we compared systemic immune responses between mice bearing high TNF producer (C5) and unmodified Meth-A cells (MO). The results indicated that the cytotoxic activity of lymphokine-activated killer cells (LAK) induced from spleen cells of mice bearing C5 was higher against both MO and C5 than that of LAK from mice bearing MO. Also, C5 was more sensitive to LAK induced from spleen cells of C5- and MO- bearing mice than MO. We also found that cytotoxic T lymphocyte from spleen cells of mice transplanted with C5 was more cytotoxic to M0 than that from mice with MO. In addition, the population of Lyt2 (CD8)-positive T cells was higher in freshly isolated spleen cells of mice transplanted with C5 than from mice with MO. Finally, we observed a higher expression of MHC class 1 antigen on C5 than on MO. These observations suggest that the augmented host systemic immunity in mice carrying TNF gene-modified Meth-A cells is one of the mechanisms of the reduced tumorigenicity of C5 and that the increased systemic immunity can be ascribed to the increased immunogenicity of the tumor cells. Thus, the use of TNF gene-modified tumor cells as vaccines appears to be promising for therapeutic and/or prophylactic application.