Interleukin-12-based immunotherapy against rat 9L glioma.
Publication/Presentation Date
4-1-1998
Abstract
OBJECTIVE: Interleukin-12 (IL-12) may be useful for immunotherapy against gliomas because it can reverse the glioma-induced suppression of T-cell proliferation and interferon-gamma production. We postulated that peripheral infusion of IL-12 along with irradiated tumor cells can lead to immunological rejection of 9L glioma.
METHODS: 9L gliosarcoma flank tumors were established in syngeneic Fischer 344 rats. Osmotic minipumps delivered IL-12 subcutaneously, and irradiated 9L cells were injected on Days 0, 3, 7, 14, and 21. Tumor volumes were measured by a blinded observer. For tumor rechallenge, animals initially cured of 9L flank tumors received either another implantation of flank tumor or a stereotactic injection of 10(6) 9L cells into the right striatum. Delayed-type hypersensitivity was measured after injecting 10(6) irradiated 9L tumor cells into the right pinnae.
RESULTS: Tumor growth curves were significantly different between treated and control animals. Among the animals that received 1 ng per day of IL-12, 40% did not develop any measurable tumors at all. A combination of irradiated 9L cells and IL-12 was necessary for optimal effect. Cured animals rejected future flank tumors. All animals rechallenged with intraparenchymal brain tumors survived, whereas control animals all died by Day 22. Delayed-type hypersensitivity measurements showed a specific and long-lasting response against 9L cells.
CONCLUSION: Continuous administration of the lymphokine IL-12, in the presence of irradiated tumor cells for antigen presentation, circumvents the need for gene transfection for generating tumor cell vaccines. We have demonstrated that the combination of IL-12 and irradiated tumor cells can lead to regression of 9L flank tumors and resistance to future flank and central nervous system tumor challenges.
Volume
42
Issue
4
First Page
850
Last Page
856
ISSN
0148-396X
Published In/Presented At
Jean, W. C., Spellman, S. R., Wallenfriedman, M. A., Hall, W. A., & Low, W. C. (1998). Interleukin-12-based immunotherapy against rat 9L glioma. Neurosurgery, 42(4), 850–857. https://doi.org/10.1097/00006123-199804000-00097
Disciplines
Medicine and Health Sciences
PubMedID
9574650
Department(s)
Department of Surgery
Document Type
Article