Prolonged survival of mice with glioma injected intracerebrally with double cytokine—secreting cells

Abstract

A novel approach toward the treatment of glioma was developed in a murine model. The genes for both interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were first transfected into a mouse fibroblast cell line that expresses defined major histocompatibility complex (MHC) determinants (H-2k). The double cytokine-secreting cells were then cotransplanted intracerebrally with the Gl261 murine glioma cell line into syngeneic C57BL/6 mice (H-2b) whose cells differed at the MHC from the cellular immunogen. The results indicate that the survival of mice with glioma injected with the cytokine-secreting allogeneic cells was significantly prolonged, relative to the survival of mice receiving equivalent numbers of glioma cells alone. Using a standard 51Cr-release assay, the specific release of isotope from labeled Gl261 cells coincubated with spleen cells from mice injected intracerebrally with the glioma cells and the cytokine-secreting fibroblasts was significantly higher than the release of isotope from glioma cells coincubated with spleen 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 specific immunocytotoxic responses after immunization with fibroblasts modified to secrete both IL-2 and IFN-gamma indicate the potential of an immunotherapeutic approach to gliomas with cytokine-secreting cells.