Pharmacologic indicators of antitumor efficacy for oncolytic virotherapy.

Abstract

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 approximately 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.

• Authors: G William Demers, Duane E Johnson, Van Tsai, Shu-Fen Wen, Erlinda Quijano, Todd Machemer, Jennifer Philopena, Murali Ramachandra, John A Howe, Paul Shabram, Robert Ralston, Heidrun Engler
• Journal: Cancer research (Cancer Res) Vol. 63 Issue 14 Pg. 4003-8 (Jul 15 2003) ISSN: 0008-5472 [Print] United States
• PMID: 12873998 (Publication Type: Journal Article)

Topics

• Adenoviridae (genetics, metabolism)
• Animals
• Genes, p53
• Humans
• Injections, Intralesional
• Injections, Intravenous
• Male
• Mice
• Prostatic Neoplasms (therapy, virology)
• Xenograft Model Antitumor Assays