2000 Fiscal Year Final Research Report Summary
IMMUNOGENE THERAPY WITH RADIATION SENSITIVE PROMOTOR IN A MOUSE BRAIN TUMOR MODEL
| Project/Area Number |
09671453
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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 | JIKEI UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
KIKUCHI Tetsuro JIKEI UNIV.SCHOOL OF MED., DEPARTMENT OF ONCOLOGY, LECTURER, 医学部, 講師 (60177798)
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| Project Period (FY) |
1997 – 2000
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| Keywords | GLIOMA / B7 / ICAM-1 / MOUSE / ASTROCYTOMA / IL-12 / IMMUNOTHERAPY |
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| Research Abstract |
Mouse glioma cells transfected with ICAM-1 grew in T-cell deficient mice but not in syngeneic mice. Vaccination with ICAM-1-transfected tumor cells markedly inhibited the growth of subcutaneously inoculated gliomas but not gliomas located in the brain. In vivo antibody ablation study revealed that CD4^+ T, CD8^+ T and NK cells were all required to produce the antitumor effect of SR/ICAM-1. Transfecting mouse tumor cell lines with the B7 gene can lead to primary tumor rejection and the establishment of protective immunity. However, some studies have shown that the B7 effect upon T-cell dependent tumor immunity is limited. Therefore, we examined the antitumor effects of recombinant IL-12 and genetically engineered glioma cells expressing B7-1 or both B7-1 and ICAM-1. Vaccination of mice with B7-1-expressing tumor cells substantially inhibited the growth of subcutaneously inoculated gliomas but not those located in the brain. Vaccination with B7-1-expressing tumor cells and systemic rIL-12 was more effective than either B7-1-expressing tumor cells or rIL-12 alone. Our murine brain tumor model also showed that vaccination with tumor cells expressing both B7-1 and ICAM-1 combined with rIL-12 prolonged survival. In vivo antibody ablation study revealed that CD8^+ T cells were required to produce the antitumor effect of SR/B7-1/ICAM-1 and rIL-12. We have demonstrated the therapeutic potential of vaccination with rIL-12 and tumor cells expressing both B7-1 and ICAM-1 in the control of glioma growth.
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