GENERATION OF TIL FROM TUMORS INDUCED BY HHV-6 DNA TRANSFECTED CELLS

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In this project, we have observed that previously non-tumorigenic NIH-3T3 cell line when transfected with human herpes virus-6 (HHV-6) genome can become tumorigenic and metastasizing in immunocompetent mice. The tumors induced by whole HHV-6 genome and a clone, pZVH14, DNA has been termed G-2T and l4-2TS respectively. We have generated tumor infiltrating lymphocytes (TIL) from these tumors and propagated them in tissue culture with recombinant IL-2. These TIL are Thy 1.2+, Lyt-2+, and L3T4- T lymphocytes and cause lysis of various targets in a 5lCr-release assay. TIL derived fro G-2TS tumor only lysed autologous target and maintain their specificity ove a 6 month period. l4-2TS tumor was not lysed by G-2TS TIL at any time point of the culture. l4-2TS TIL, however, lysed autologous as well as allogeneic (including Yac-1 lymphoma) target and after several days in culture lost their lytic capability of autologous targets. These TIL, however, lysed yac-I target until 73 days of culture. These studies indicate that HHV-6 virus has tumorigenic potential in mice and hosts can mount an immune response to these tumors by infiltrating cytotoxic T lymphocytes. These TIL may be useful in the identification of tumor associated antigen(s). This project is still active.