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