Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter

M. Ahn, S. J. Lee, Xiaochun Li, J. A. Jiménez, Y. P. Zhang, K. H. Bae, Y. Mohammadi, Chinghai Kao, Thomas Gardner

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 μg ml-1), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalCancer Gene Therapy
Volume16
Issue number1
DOIs
StatePublished - Jan 2009

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Genetic Therapy
Suicide
Prostatic Neoplasms
Neoplasms
Androgens
Prodrugs
Adenoviridae
Therapeutics
Cell Line
Clinical Trials, Phase I
Viral Genes
Thymidine Kinase
Neoplasm Genes
Therapeutic Uses
Simplexvirus
Nude Mice
Prostate
Neoplasm Metastasis
Safety
Drug Therapy

Keywords

  • HSV-TK
  • M6 prostate-specific promoter
  • Prostate cancer
  • Suicide gene therapy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Molecular Biology

Cite this

Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter. / Ahn, M.; Lee, S. J.; Li, Xiaochun; Jiménez, J. A.; Zhang, Y. P.; Bae, K. H.; Mohammadi, Y.; Kao, Chinghai; Gardner, Thomas.

In: Cancer Gene Therapy, Vol. 16, No. 1, 01.2009, p. 73-82.

Research output: Contribution to journalArticle

Ahn, M. ; Lee, S. J. ; Li, Xiaochun ; Jiménez, J. A. ; Zhang, Y. P. ; Bae, K. H. ; Mohammadi, Y. ; Kao, Chinghai ; Gardner, Thomas. / Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter. In: Cancer Gene Therapy. 2009 ; Vol. 16, No. 1. pp. 73-82.
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