PROLONGED SURVIVAL OF MICE WITH GLIOMA INJECTED INTRACEREBRALLY WITH DOUBLE CYTOKINE-SECRETING CELLS

A novel approach toward the treatment of glioma was developed in a mur ine model. The genes for both interleukin-2 (IL-2) and interferon-gamm a (IFN-gamma) were first transfected into a mouse fibroblast cell line that expresses defined major histocompatibility complex (MHC) determi nants (H-2(k)). The double cytokine-secreting cells were then cotransp lanted intracerebrally with the G1261 murine glioma cell line into syn geneic C57BL/6 mice (H-2(b)) whose cells differed at the MHC from the cellular immunogen. The results indicate that the survival of mice wit h glioma injected with the cytokine-secreting allogeneic cells was sig nificantly prolonged, relative to the survival of mice receiving equiv alent numbers of glioma cells alone. Using a standard Cr-51-release as say, the specific release of isotope from labeled G1261 cells coincuba ted with spleen cells from mice injected intracerebrally with the glio ma cells and the cytokine-secreting fibroblasts was significantly high er than the release of isotope from glioma cells coincubated with sple en cells from nonimmunized mice. The cellular antiglioma response was mediated by natural killer/lymphokine-activated killer and Lyt-2.2(+) (CD8(+)) cells. The increased survival of mice with glioma and the spe cific immunocytotoxic responses after immunization with fibroblasts mo dified to secrete both IL-2 and IFN-gamma indicate the potential of an immunotherapeutic approach to gliomas with cytokine-secreting cells.