1995 Fiscal Year Final Research Report Summary
Experimental Viral Therapy for the Treatment of Malignant Glioma Using Recombinant Herpes Simplex Virus Type 1
| Project/Area Number |
06454418
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Saga Medical School |
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Principal Investigator |
ABE Masamitsu Saga Medical School, Faculty of Medicine Associate Professor, 医学部, 助教授 (20136427)
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| Co-Investigator(Kenkyū-buntansha) |
MINETA Toshihiro Saga Medical School, Faculty of Medicine Instructor, 医学部, 助手 (20264187)
SHIRAISHI Tetsuya Saga Medical School, Faculty of Medicine Instructor, 医学部, 助手 (70206275)
MOMOZAKI Nobuaki Saga Medical School, Faculty of Medicine Assistant Professor, 医学部, 講師 (30239587)
TABUCHI Kazuo Saga Medical School, Faculty of Medicine Professor, 医学部, 教授 (50116480)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Glioma / Herpes simplex virus / Mutant virus / Gene insertion / Antiviral agent / Viral therapy |
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| Research Abstract |
We are exploring a novel experimental treatment for malignant brain tumors utilizing a genetically engineered attenuated replication-competent herpes simplex virus type 1 (HSV-1). Our previos studies demonstrated that a thymidine kinase-deficient HSV-1 mutant(dlsptk), could destroy human glioma cells, allowing for replication in dividing tumor cells but not in non-dividing cells. We hypothesized that such HSV-1 mutants might replicate in actively growing tumor cells and effectively kill malignant brain tumors while sparing normal brain cells. In order for this therapy to become an effective clinical choice, we have created a multiple deletion mutant of herpes simple virus type 1 which has favorable properties for the treatment of human malignant brain tumors. This mutant, termed G207, has 1.0 kb deletions at both gamma34.5 loci and a lacZ gene insertion inactivating the ICP6 locus. G207 causes a spreading infection killing human glioma cells in monolayr cultures. In nude mice harboring subcutaneous or intracerebral U-87MG gliomas, intraneoplastic inoculation of G207 causes decreased tumor growth and/or prolonged survival. G207 is avirulent upon intracerebral inoculation of mice and HSV sensitive non-human primates. These results have stimulated interest in its possible clinical trial for the treatment of malignant brain tumors.
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