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[Cancer Research 59, 410-413, January 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 410-413, January 15, 1999]
© 1999 American Association for Cancer Research

Experimental Therapeutics

Therapy of Colon Cancer with Oncolytic Adenovirus Is Enhanced by the Addition of Herpes Simplex Virus-thymidine kinase

Oliver Wildner1, R. Michael Blaese and John C. Morris

Clinical Gene Therapy Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland 20892-1851

A major obstacle to the successful application of suicide gene therapy strategies that rely on in situ transduction of tumor cells is the poor distribution of the vector throughout the tumor mass. To address this problem, we evaluated the use of Ad.TKRC, an E1b Mr 55,000 deleted replicating adenoviral vector engineered to express the herpes simplex virus type 1 thymidine kinase gene (HSV-tk) in combination with ganciclovir (GCV) as a treatment for human colon cancer xenografts in nude mice. We compared the efficacy of this system with that of a standard replication-deficient adenovirus expressing HSV-tk (Ad.TK) in mice bearing LS180 tumors. In this system, Ad.TKRC alone was as effective as a traditional Ad.TK vector in combination with GCV. The addition of GCV significantly enhanced the antitumor effect of Ad.TKRC. Furthermore, we demonstrated that the survival of HT-29 human colon cancer xenografted mice treated with Ad.TKRC and GCV was prolonged compared with Ad.TKRC alone or with administration of a single cycle of topotecan. These data demonstrate that the addition of direct viral oncolysis to the HSV-tk/GCV suicide gene system resulted in a striking improvement in treatment efficacy and that it may offer advantages over the use of chemotherapeutic agents for treatment of localized disease.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.