FIBROBLASTS GENETICALLY-ENGINEERED TO SECRETE CYTOKINES SUPPRESS TUMOR-GROWTH AND INDUCE ANTITUMOR IMMUNITY TO A MURINE GLIOMA IN-VIVO

THE GENES FOR interleukin (IL)-2, interferon (IFN)-gamma, or both IL-2 and IFN-gamma were introduced into a mouse fibroblast cell line (LM) expressing defined major histocompatibility complex determinants (H-2( k)). The cytokine-secreting cells were then co-transplanted with the G l261 murine glioma cell line (H-2(b)) into syngeneic C57BL/6 mice that differed at the major histocompatibility complex from the cytokine-se creting cells. The period of survival of mice with glioma treated with IL-2- or IL-2/IFN-gamma-secreting allogeneic cells was significantly prolonged (P < 0.025) relative to the survival of mice receiving equiv alent numbers of tumor cells alone or mice with glioma treated with no nsecreting fibroblast (LM) cells. Gliomas in the treated mice had an e xtensive lymphocytic cell infiltrate. Using a Cr-51 release assay, the specific release of isotope from labeled Gl261 cells co-incubated wit h spleen cells from mice injected with the glioma cells and IL-2-secre ting fibroblasts was higher (P < 0.001) than the release from glioma c ells co-incubated with spleen cells from nonimmunized mice. Significan tly higher levels of release (P < 0.005) were found in the group immun ized with fibroblasts secreting both IL-2 and lFN-gamma. Based upon th e effect of monoclonal antibodies for T-cell subsets on the antiglioma response, the immunity was mediated predominantly by natural killer/l ymphokine-activated killer cells.