1999 Fiscal Year Final Research Report Summary
Basic Research into Clinical Application of Gene Therapy for Prostate Cancer
| Project/Area Number |
09671628
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kobe University School of Medicine |
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Principal Investigator |
GOTOH Akinobu Kobe Univ. Sch. of Med., Dept. of Urology, Assistant Professor, 医学部, 助手 (70283885)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Isao Kobe Univ. Sch. of Med., Dept. of Urology, Assistant Professor, 医学部, 助手 (10263378)
OKADA Hiroshi Kobe Univ. Hospital, Dept. of Urology, Lecturer, 医学部・附属病院, 講師 (00177057)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Prostate cancer / Prostate Specific Antigen(PSA) / tissue specific / promoter / Thymidine Kinase(TK) / Adenovirus / Gene Therapy / Clinical Application |
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| Research Abstract |
Treatment of prostate cancer in the past has involved surgery, radiation therapy, hormonal and/or chemotherapy. Recently, gene therapy was introduced as a new therapeutic modality for the treatment of both localized and metastatic diseases. We have defined the androgen responsiveness and status of Prostate Specific Antigen(PSA) secretion of prostate cancer cells as well as non prostatic cells transduced with PSA promoter reporter constructs. Androgen-independent (AI) human prostate cancer remains a lethal phenotype for which there is no effective therapy. AI prostate cancer produces and secretes large amounts of PSA at both primary and metastatic sites. The aim of this investigation is to explore the use of the PSA promoter as a mean of prostate cell specific expression of a toxic gene thymidine kinase(TK) to an AI PSA-producing human prostate cancer cell line in vitro and in vivo. We compared the therapeutic efficacy of the PSA promoter in several human cell lines in vitro and in vivo. An adenovirus vector carrying human herpes simplex thymidine kinase(TK) gene under control of the PSA promoter (Ad-PSA-TK) was generated to target PSA-producing AI prostate cancer cells. The PSA promoter is a strong candidate for high, specific expression of therapeutic genes in PSA producing prostate cancer cells. Upon the administration of acyclovir, Ad-PSA-TK efficiently killed the AI PSA-producing human prostate cancer cells in vitro and in vivo.
I discuss the importance of tissue specific promoter system for using gene therapy of prostate cancer, and summarize the potential for clinical application of gene therapy to AI prostate cancer.
This our strategy potentially can be used in combination with current therapeutic modalities to achieve more effective tumor cell-kill with much reduced toxicity.
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[Publications] A.Gotoh, S.C.Ko, T.Shirakawa, J.Cheon, C.Kao, T.Miyamoto, T.A.Gardner, L.J.Ho, C.B.J.Cleutjens, J.Trapman, F.L.Graham, L.W.K.Chung: "Development of prostate-specific antigen promoter-based gene herapy for androgen-independent human prostate cancer"Journal of Urology. 160. 220-229 (1998)
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