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

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

J Neurosurg. 1995 Dec;83(6):1038-44. Unique Identifier : AIDSLINE MED/96086871
Lichtor T; Glick RP; Kim TS; Hand R; Cohen EP; Division of Neurosurgery, Cook County Hospital, Chicago,; Illinois, USA.

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.

Keywords: Animal Brain Neoplasms/MORTALITY/*THERAPY Cell Line Cytotoxicity, Immunologic CD8-Positive T-Lymphocytes/IMMUNOLOGY Disease Models, Animal Female Fibroblasts/*SECRETION/TRANSPLANTATION Glioma/MORTALITY/*THERAPY Interferon Type II/*SECRETION/THERAPEUTIC USE Interleukin-2/*SECRETION/THERAPEUTIC USE Killer Cells, Lymphokine-Activated/IMMUNOLOGY Killer Cells, Natural/IMMUNOLOGY Mice Mice, Inbred C57BL Spleen/CYTOLOGY/IMMUNOLOGY Support, U.S. Gov't, P.H.S. Time Factors Transfection JOURNAL ARTICLE
960330
M9630679

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