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Oncolytic viral therapy for disseminated peritoneal ovarian cancer using a novel replication-competent herpes simplex virus type 1 mutant in mice.

Research Project

Project/Area Number 13671760
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionAichi Cancer Center

Principal Investigator

NAWA Akihiro  Aichi Cancer Center, Investigator, 研究所, 研究員 (90242859)

Co-Investigator(Kenkyū-buntansha) NISHIYAMA Yukihiro  Nagoya University, Graduate School of Medicine, Laboratory of Virology professor, 大学院・医学研究科ウイルス感染, 教授 (60115615)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsreplication-competent / herpes simplexvirus type1 mutant / ovarian cancer / peritoneally disseminated neoplasm / mouse model / syncytial formation / apoptosis / immuno-competent mouse / 増殖型HSVI変異株
Research Abstract

We prepared two attenuated mutant HSV-1 strains. One is an HSV-1 mutant, hrR3, and another is a new replication competent HSV-1 mutant, HR522 ; this virus, expressing the lacZ reporter gene, induces syncytium formation in infected cells. We compared the efficacy of HR522 with Taxol and hrR3 in the treatment of nude mice harboring human ovarian cancer cells. We also examined the effect of the prodrug ganciclovir (GCV) on the treatment mediated by these HSVs. The survival of mice treated with a high titer hrR3 (5x10^7 plaque-forming units ; PFU) was significantly prolonged as compared to the group given Taxol (p<0.0001 ; Log-Rank test). Although the survival of mice treated with high titer HR522 (5x10^7 PFU) was not significantly prolonged compared with Taxol-treated group (p=0.212 ; Log-Rank test), GCV markedly enhanced the efficacy of HR522 administration (p<0.005 ; vs Taxol ; Log-Rank test). The lacZ gene product, visualized using 5-brorno-4-chrolo-3-indoryl-β-D- galactopyranoside (X-gal) histochemistry, was detected in HR522-treated tumors in areas also exhibiting apoptotic changes. Another study demonstrated that a clonal derivative of HSV-1 strain HF done 10 very effectively treated peritoneally disseminated neoplasm in an immunocompetent animal model and that all of survived mice acquired resistance to rechallenge of tumor cells. HF clone 10 induces syncytia formation in vitro. A sequential administration ofHF clone 10 attained a long-term survival over 90 days after tumor injection in 8 of the 9 treated mice without any signs of diseases. The results suggested that treatment of peritoneally disseminated tumor with HF clone 10 induced a specific anti-tumor immune response. We found that clone 10 has a deletion of 39kbp in the right end of UL and UL/IRL junction, resulting in the loss of UL 56 expression. Moreover, a 23kbp deletion and extensive rearrangement were observed in the left end of the genome.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Takakuwa H.: "Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent mice"Archives of Virology. 148. 813-825 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takakuwa H.: "Oncolytic viral therapy using a spontaneously generated herpes simplex virus type1 variont for disseminated peritoneal tumor in immunocompetent mice"Archives of Virology. 148. 813-825 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takakuwa H, Nawa A, Nishiyama Y, et al.: "Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for peritoneally disseminated tumor in immunocompetent mice"Archives of Virology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Nicolson GL, Nawa A, et al.: "Tumor metastasis-associated human MTA1 gene and its MTA1 protein product: role in epithelial cancer cell invasion, proliferation and nuclear regulation"Clinical experimental metastasis. (in press).

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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