• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Gene therapy specific for lung cancer using cell-type specific promoter

Research Project

Project/Area Number 09670612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionOSAKA UNIVERSITY

Principal Investigator

HAYASHI Seiji  Osaka University Medical School, Depariment of Medicine III, 医学部, 講師 (70218577)

Co-Investigator(Kenkyū-buntansha) KIJIMA Takashi  Osaka University Hospital, Department of Medicine III,Medical Staff, 医学部・附属病院, 医員
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsLung cancer / HSV-tk / CEA promoter / Cre / loxP system / myc oncogene / ganciclovir (GCV) / nonproliferating adenoviral vector / 非増殖型アデノウイルスベクター
Research Abstract

(1) Gene therapy specific for CEA-producing lung cancer
Rejection of CEA-producing tumors was not observed by intra-tumoral injection with a recombinant adenoviral vector (Ad.) expressing the HSV-tk gene under the CEA promoter (Ad.CEA-TK) followed by ganciclovir (GCV) treatment in vivo.It is conceivable that the low activity of the CPA promoter results in insufficient expression of the HSV-tk gene in cancer cells as well as in insignificant antitumor effects.To obtain enhanced expression of the HSV-tk gene exclusively in tumor cells and subsequent significant in vivo antitumor effects, we applied the Cre/loxP system to HSV-tk/GCV therapy for CEA-producing cancer.We constructed an Ad producing Cre recombinase driven by the CEA promoter (Ad.CEA-Cre) and another Ad designed for inducible expression of the HSV-tk gene by Cre (Ad.CAG-loxP-TK).Co-infection by these Ads rendered a human CEA-producing cancer cell line 8.4-fold more sensitive to GCV compared with infection by Ad.CEA-TK alone.On … More the other hand, co-infection with these Ads did not significantly change GCV sensitivity of CEA-non-producing cells.Intra-tumoral injection of Ad.CEA-Cre combined with Ad.CAG-loxP-TK followed by GCV treatment completely eradicated CEA-producing tumors established in the subcutis of 6 out of 7 athymic mice, whereas injection of Ad.CEA-TK alone with GCV administration at most retarded the growth of inoculated tumors.These results suggest distinct advantages of the Cre/loxP system applied in the conventional cell type-specific gene therapy against cancer.We are now evaluating the efficacy and side effects of this system in the peritonitis carcinomatosa model in mice, mimicking pleuritis for lung cancer in future clinical applications to human beings.
(2) Gene therapy specific for Myc-overexpressing small cell lung cancer (Myc-SCLC)
We previousely reported that an Ad. containing the HSV-tk gene ligated with the Myc-binding motif (Ad.Myc-TK) showed a cell-type specific expression of the HSV-tk gene in Myc-SCLC cell lines.We analyzed the efficacy of the intraperitoneal injection of Ad.Myc-TK followed by GCV treatment on Myc-SCLC inoculated in the peritoneal cavity of athymic mice.This treatment successfully reduced the weight of tumors to one fourteenth of that of untreated mice and completely eradicated tumors in 2 of 8 mice. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] Kumagai T et al.: "Eradication of My c-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements." Canser Res. 15 ; 56(2). 354-358 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osaki T et al.: "Gene therapy for carcinoembryonic an tigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene." Cancer Res. 15 ; 54(20). 5258-61 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tachibana I et al.: "A 100-k Da protein tyrosine phosphorylation is concurrent with beta l integrin-mediated morphological differentiation in neuroblastoma and small cell lung cancer cells." Exp Cell Res. 15 ; 227(2). 230-9 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueno K et al.: "Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer." Hum Genet. 102(1). 63-8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumagai T et al.: "Eradication of Myc-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements." Cancer Res Jan. 15 ; 56(2). 354-358 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osaki T et al.: "Gene therapy for carcinoembryonic antigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene." Cancer Res Oct. 15 ; 54(20). 5258-61 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tachibana I et al.: "A 100-kDa protein tyrosine phosphorylation is concurrent with beta 1 integrin-mediated morphological differentiation in neuroblastoma and small cell lung cancer cells." Exp Cell Res Sep. 15 ; 227(2). 230-239 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ueno K et al.: "Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer." Hum Genet Jan. 102(1). 63-8 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kumagai T et al.: "Eradication of My c-overexpressing small cell lung cancer cells transfected with herpes simplex virus thymidine kinase gene containing Myc-Max response elements." Cancer Res. 15;56(2). 354-358 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Osaki T et al.: "Gene therapy for carcinoem bryonic an tigen-producing human lung cancer cells by cell type-specific expression of herpes simplex virus thymidine kinase gene." Cancer Res. 15;54(20). 5258-5261 (1994)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tachibana I et al.: "A 100-kDa protein tyrosine phosphorylation is concurrent with beta 1 Integrin-mediated morphological differentiation in neuroblastoma and small cell lung cancer cells." Exp Cell Res. 15;227(2). 230-239 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ueno K et al.: "Cloning and tissue expression of cDNAs from chromosome 5q21-22 which is frequently deleted in advanced lung cancer." Hum Genet. 102(1). 63-68 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kumagai.T.et al.: "Eradication of Myc-overexpessing small cell lung cancer cells transfected with Herpes Simplex virus thymidine kinase gene containing Myc-Max response elements." Cancer Res.56. 354-358 (1996)

    • Related Report
      1997 Annual Research Report

URL: 

Published: 1997-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi