Development of tumor immunotherapy by vaccinated cancer cells

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The immunogenicity of human cancer cells is generally very low. Poorly immunogenic animal tumor cells can be converted into highly immunogenic tumors by several techniques. The purpose of this studies is to investigate whether UV-B-irradiated, IL-2 genetransduced, or IL-12 genetransduced human cancer cells are more immunogenic than untreated tunor cells with respect to MHC antigen expression, and the ability of inducing cytotoxic T lymphocyte (CTL) activity. UV-B radiation respectively decreased or increased MHC class I expression of freshly isolated tumor cells or cultured tumor cells, and also decreased MHC class I expression of starved cultured tumor cells. It increased the ability of both freshly isolated and cultured tumor cells to induce CTL activity from PBMC against untreated autologous tumor cells. These results indicated that UV radiation increased the ability of tumor cells to induce CTL activity without a corresponding effect on MHC antigen expression. Human renal cell carc … More inoma (RCC) cells transduced with human IL-2 gene (RCC-IL-2) stimulated PBMC to demonstrate LAK activity, and also stimulated autologous TILs to proliferate and exhibit cytotoxicity relatively restricted to autologous tumor cells. In contrast, both parental RCC and RCC transduced with neomycin gene alone failed to induce these activities. These results indicate that RCC-IL-2 cells are more potent than the other RCC cells with regard to inducing cytotoxic lymphocytes against autologous tumor cells. IL-12 genetransduced squamous cell carcinoma (IL-12-SCC) cells displayd enhanced expression of MHC class I antigen to induce autologous CTL against autologous SCC cells more potently than parental, non-IL-12 gene-transduced SCC cells. The main effector cells that exhibited relatively specific cytolysis against parental SCC cells were CD16+CD56+cells. In addition IL-12 gene-SCC cells were more susceptible to those effector cells than parental SCC cells. These results suggest that IL-12 may be able to maintain NK-cells for a long -term to display major, specific cytotoxicity and IL-12-SCC cells are well-recognized to lyse by those effector cells. In summary, UV radiation, IL-2, or IL-12 gene-transduction are potent methods to change tumor cells to induce CTL,or activated NK-cells with or without a corresponding effects on MHC antigen expression. Less