Prospects for herpes-simplex-virus thymidine-kinase and cytokine gene transduction as immunomodulatory gene therapy for prostate cancer

Waleed Hassan, Michael A. Sanford, Savio L C Woo, Shu Hsia Chen, Simon J. Hall

Research output: Contribution to journalArticle

Abstract

In completed and ongoing clinical trials, adenovirus-mediated (Ad.) expression of herpes-simplexvirus thymidine-kinase (HSV-tk) gene transduction followed by ganciclovir (GCV) therapy has produced limited toxicity and evidence of antitumor activity following injection of the prostate. Furthermore, this system has been shown to direct systemic antitumor activity in several experimental cancer models, including that of prostate cancer, which may serve as the basis for in-situ immunomodulatory gene therapy. In a mouse model of prostate cancer, natural killer (NK) cells have been identified as the mediator of antimetastatic activity following Ad.HSV-tk + GCV, resulting in the combination of Ad.HSV-tk and adenovirus-mediated expression of interleukin 12 (Ad.IL-12) to exploit this cytokine's ability to enhance NK proliferation and cytotoxicity. Combination therapy demonstrated superior local and systemic growth suppression over that obtained with either therapy alone. Importantly, when the metastatic tumor burden was increased to an extent that negated the growth-suppressive activity directed by Ad.HSVtk + GCV or Ad.IL-12 alone, combination therapy continued to demonstrate significant growth suppression. Examination of tumor-infiltrating lymphocytes documented enhanced NK lytic activity following combination therapy. Therefore, it appears that the combination of Ad.HSV-tk and Ad.IL-12 should be validated in a clinical trial for the treatment of prostate cancer.

Original languageEnglish (US)
Pages (from-to)130-135
Number of pages6
JournalWorld Journal of Urology
Volume18
Issue number2
StatePublished - 2000
Externally publishedYes

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Immunomodulation
Thymidine Kinase
Simplexvirus
Adenoviridae
Genetic Therapy
Prostatic Neoplasms
Cytokines
Genes
Ganciclovir
Interleukin-12
Therapeutics
Growth
Clinical Trials
Tumor-Infiltrating Lymphocytes
Tumor Burden
Natural Killer Cells
Prostate
Theoretical Models
Injections

ASJC Scopus subject areas

  • Urology

Cite this

Prospects for herpes-simplex-virus thymidine-kinase and cytokine gene transduction as immunomodulatory gene therapy for prostate cancer. / Hassan, Waleed; Sanford, Michael A.; Woo, Savio L C; Chen, Shu Hsia; Hall, Simon J.

In: World Journal of Urology, Vol. 18, No. 2, 2000, p. 130-135.

Research output: Contribution to journalArticle

Hassan, Waleed ; Sanford, Michael A. ; Woo, Savio L C ; Chen, Shu Hsia ; Hall, Simon J. / Prospects for herpes-simplex-virus thymidine-kinase and cytokine gene transduction as immunomodulatory gene therapy for prostate cancer. In: World Journal of Urology. 2000 ; Vol. 18, No. 2. pp. 130-135.
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