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

• Published in: Journal of neurosurgery Vol. 83; no. 6; pp. 1038 - 1044
• Main Authors: LICHTOR, T, GLICK, R. P, TAE SUNG KIM, HAND, R, COHEN, E. P
• Format: Journal Article
• Language: English
• Published: Park Ridge, IL American Association of Neurological Surgeons 01-12-1995
• Subjects: AIDS/HIV; Animals; Biological and medical sciences; Brain Neoplasms - mortality; Brain Neoplasms - therapy; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cytotoxicity, Immunologic; Disease Models, Animal; Female; Fibroblasts - secretion; Fibroblasts - transplantation; Glioma - mortality; Glioma - therapy; Interferon-gamma - secretion; Interferon-gamma - therapeutic use; Interleukin-2 - secretion; Interleukin-2 - therapeutic use; Killer Cells, Lymphokine-Activated - immunology; Killer Cells, Natural - immunology; Medical sciences; Mice; Mice, Inbred C57BL; Neurology; Spleen - cytology; Spleen - immunology; Time Factors; Transfection; Tumors of the nervous system. Phacomatoses; Intracranial; Nervous system diseases; Cytokine; Rodentia; Malignant tumor; Survival; Cerebral disorder; Malignant glioma; Vertebrata; Mammalia; Interleukin 2; Mouse; Animal; Central nervous system disease; Intracerebral administration; Gene therapy; Gamma interferon
• ISSN: 0022-3085; 1933-0693
• DOI: 10.3171/jns.1995.83.6.1038

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.