1998 Fiscal Year Final Research Report Summary
Basic Research for The Immuno-genetherapy of Brain Tumors
| Project/Area Number |
09671409
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
IWADATE Yasuo CHIBA UNIVARSITY,NEUROSURGERY,ASSISTANT, 医学部, 助手 (70272309)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAURA Akira CHIBA UNIVERSITY,NEUROSURGERY,PROFESSOR, 医学部, 教授 (40009717)
NAMBA Hiroki CHIBA CANCER CENTER,NEURISURGERY, 医長
TAGAWA Masatoshi CHIBA CANCER CENTER,PATHOLOGY, 研究局, 部長
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| Project Period (FY) |
1997 – 1998
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| Keywords | gene therapy / brain tumor / interleukin-2 / immunity |
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| Research Abstract |
Enhancement of host antitumor response using cytokine-producing tumor cells has been investigated in various types of cancers. The central nervous system, however, shows tolerance for activated immune reactions, and this relative unresponsiveness may lessen the efficacy of immunotherapy for brain tumors. Using interleukin-2 (IL-2)-producing 9L rat gliosarcoma cells (9L/IL-2), we examined whether secretion of IL-2 from subcutaneous (s.c.) and/or intracranial (i.c.) tumors can elicit augmented immunological response to brain tumors. Syngeneic rats could reject 9L/IL-2 cells inoculated s.c., but developed i.c. 9L/IL-2 tumors. The growth of i.c. 9L/IL-2 tumors was, however, significantly retarded compared with that of wild-type tumors. The growth of i.c. wild-type tumors was also suppressed, when the rats concurrently received 9L/IL-2 cells s.c.. Moreover, most of the rats which inoculated i.c. with 9L/IL-2 cells did not developed brain tumors, when concurrently injected s.c. with 9L/IL-2 cells. Immunohistochemical analysis revealed that migration of CD4- positive T cells, CD8-positive T cells, monocytes/ microglias and macrophages in i.c. 9L/IL-2 tumors was less notable than that in s.c. 9L/IL-2 tumors, but was more significant than that in i.c. wild-type tumors. When the rats were inoculated s.c. with 9L/IL-2 cells, the cellular infiltration into intracranial 9L/IL-2 tumors was markedly augmented to a similar level as found in s.c. 9L/IL-2 tumors. The present study may raise a possibility of a therapeutic strategy for brain tumors by the combinatory expression of IL-2 gene using s.c. immunization followed by the direct gene transfer into brain tumors.
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[Publications] Iwadate, Y., Namba, H., Tagawa, M., Takenaga, K., Sueyoshi., Sakiyama, S.: "Induction of acquired immunity in rats that have eliminated intracranial gliosarcoma cells by the expression of herpes simplex virus-thymidine kinase gene and ganciclovir administration." Oncology. 54. 329-334 (1997)
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