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1997 Fiscal Year Final Research Report Summary

Experimental study of gene therapy for malignant glial cells by transfection with IL-12 gene -using SCID mouse model imitating human being-

Research Project

Project/Area Number 08671609
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionJichi Medical School

Principal Investigator

HASHIMOTO Masaaki  JIchi Medical School, Neurosurgery, assistant professor, 医学部, 講師 (60221496)

Co-Investigator(Kenkyū-buntansha) HATAKE Kiyohiko  Jichi Medical School, Hematology, associate professor, 医学部, 助教授 (80192699)
NAGAI Mutsumi  Jichi Medical School, Neurosurgery, assistant, 医学部, 病院助手 (10265259)
Project Period (FY) 1996 – 1997
KeywordsIL-12 gene / malignant glioma / SCID mouse / experimenta model imitating / human being / gene therapy / ex vivo
Research Abstract

1.Making an Experimental model imitating human being
After the intraperitoneal administration of SCID mouse with human mononuclear cells, these human mononuclear cells were detected until 3 weeks. Administration of human IL-2 simultaneously prolonged the life span of human mononuclear cells about 1 or 2 weeks. It suggests that human IL-2 activated human NK cells and T cells. We don't know why some SCID mouse died after the administration early. So it is necessary for experimental model to use the other cytokines.
2.IL-12 expression in patients with malignant glioma, having beta-IFN therapy
For patients with malignant astrocytoma or glioblastoma, we underwent immunotherapy with beta-IFN (3 million unit) every other day. During the therapy, NK activity, LAK activity and IL-12 expression were measured. However we cannot find NK activity, LAK activity and IL-12 expresion significantly.
3.Transfection of IL-12 gene (p35, p40) into malignant glioma cell line
IL-12 gene could not be successfully introdued into malignant glioma cell line. Both subunits of p35 and p40 are nessesary for active type of IL-12. So we did double transfection of P35 and p40 with electroporation. Now we investigate to find the surest way of induction of IL-12. On the other hand, in vitro study IL-12 induced a considerable antitumor effect from human mononuclear cells on human glioma cell line, even compared with IL-2. However, for the purpose of clinical trial of IL-12, it is important to establish the ex vivo model.

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Published: 1999-03-16  

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