TY - JOUR
T1 - Prospects for herpes-simplex-virus thymidine-kinase and cytokine gene transduction as immunomodulatory gene therapy for prostate cancer
AU - Hassan, Waleed
AU - Sanford, Michael A.
AU - Woo, Savio L.C.
AU - Chen, Shu Hsia
AU - Hall, Simon J.
N1 - Funding Information:
Acknowledgements The authors would like to thank Dr. Timothy C. Thompson for providing the RM-1 mouse prostate-cancer cell lines used in these studies. This work was supported in part by grant M01 RR00071 to the Mount Sinai General Clinical Research Center from the National Center for Research Resources, NIH; the Edwin Beer Award, New York Academy of Medicine; and the National Kidney Foundation of New York/New Jersey.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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.
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U2 - 10.1007/s003450050185
DO - 10.1007/s003450050185
M3 - Article
C2 - 10854148
AN - SCOPUS:0034168678
VL - 18
SP - 130
EP - 135
JO - World Journal of Urology
JF - World Journal of Urology
SN - 0724-4983
IS - 2
ER -