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[Cancer Research 63, 4003-4008, July 15, 2003]
© 2003 American Association for Cancer Research

Experimental Therapeutics

Pharmacologic Indicators of Antitumor Efficacy for Oncolytic Virotherapy

G. William Demers1, Duane E. Johnson, Van Tsai, Shu-Fen Wen, Erlinda Quijano, Todd Machemer, Jennifer Philopena, Murali Ramachandra, John A. Howe, Paul Shabram, Robert Ralston and Heidrun Engler

Canji, Inc., San Diego, California 92121

Central to the development of oncolytic virotherapies for cancer will be a better understanding of the parameters that influence the outcome of virotherapy to treat disseminated cancer by i.v. administration versus regional disease by local treatment. Intratumoral administration of 01/PEME, an oncolytic adenovirus, required ~1000-fold less dose than i.v. administration to induce similar tumor growth inhibition. Despite the short (<10 min) circulating half-life of the virus DNA, we could monitor virus distribution to the tumor site and observed virus replication by >1000-fold increase in virus DNA copies over time. There were doses of 01/PEME for which the virus DNA concentration in the tumor increased over time but did not result in antitumor efficacy. Oncolytic virus replication at a tumor site may not be a relevant indication of antitumor efficacy. Efficient distribution to the tumor site may be one of the most critical parameters for antitumor efficacy with oncolytic virotherapy.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Copyright © 2003 by the American Association for Cancer Research.