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1995 Fiscal Year Final Research Report Summary

Experimental Viral Therapy for the Treatment of Malignant Glioma Using Recombinant Herpes Simplex Virus Type 1

Research Project

Project/Area Number 06454418
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Cerebral neurosurgery
Research InstitutionSaga Medical School

Principal Investigator

ABE Masamitsu  Saga Medical School, Faculty of Medicine Associate Professor, 医学部, 助教授 (20136427)

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)
Project Period (FY) 1994 – 1995
KeywordsGlioma / Herpes simplex virus / Mutant virus / Gene insertion / Antiviral agent / Viral therapy
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.

  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Mineta,T.: "Treatment of Malignant Gliomas Using Ganciclovir-Hypersensitive,Ribonucleotide Reductase-Deficient Herpes Simplex Viral Mutant." Cancer Res. 54. 3963-3966 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takmamiya,Y.: "AGM-1470 Inhibits the Growth of Human Glioma Cells in viro and in vivo." Neurosurgery. 34. 869-875 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ahmad,S.: "Antisense Expression of Protein Kinase Ca Inhibits the Growth and Tumorigenicity of Human Glioblastoma Cells." Neurosurgery. 35. 904-909 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mineta,T.: "Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas." Nature Medicine. 1. 938-943 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yazaki,T.: "Inhibition of angiogenesis and growth of human non-malignant and malignant meningiomas by TNP-470." J Neuro-oncol.23. 23-29 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 峯田寿裕: "組み換え型単純ヘルペスウイルス1型による悪性脳腫瘍の実験的治療。" 脳神経外科. 23. 285-292 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mineta,T.: "Braim Tumor Research and Therapy Nagai,M.Ed." Springer-Verlag Tokyo, 6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mineta, T., Rabkin, S.D.and Martuza, R.L.: "Treatment of Malignant Gliomas Using Ganciclovir-Hypersensitive, Ribonucleotide Reductase-Deficient Herpes Simplex Viral Mutant." Cancer Res.54. 3963-3966 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takamiya, Y., Brem, H., Ojeifo, J., Minata, T.and Martuza, R.L.: "AGM-1470 Inhibits the Growth of Human Glioma Cells in viro and vivo" Neurosurgery. 34. 869-875 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ahmad, S., Mineta, T., Martuza, R.L.and Glazer, R.I.: "Antisense Expression of Protein Kinase Ca Inhibits the Growth and Tumorigenicity of Human Glioblastoma Cells" Neurosurgery. 35. 904-909 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Toshihiro Mineta, Samuel D.Rabkin, Takahito Yazaki, William D.Hunter, and Robert L.Martuza: "Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas" Nature Medicine. 1. 938-943 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahito Yazaki, Yoshiaki Tajamiya: "Penelope Costello, Toshihiro Mineta, Anil G.Menon, Samuel D.Rabkin, and Robert L.Martuza : Inhibition of angiogenesis and growth of human non-malignant and malignant meningiomas by TNP-470" J Neuro-oncol. 23. 23-29 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mineta, T., Martuza, R.L., Tabuchi, K.: "Gene therapy for brain tumors : Experimental treatment of malignant brain tumors using recombinant herpes simplex virus type 1" Neurol.Surg.(Jpn). 23. 285-292 (1995)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1997-03-04  

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