title: 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.affiliation: Canji, Inc., San Diego, California 92121, USA. bill.demers@canji.com
authors.forename: G William
authors.initials: GW
authors.lastname: Demers
authors.forename: Duane E
authors.initials: DE
authors.lastname: Johnson
authors.forename: Van
authors.initials: V
authors.lastname: Tsai
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Wen
authors.forename: Erlinda
authors.initials: E
authors.lastname: Quijano
authors.forename: Todd
authors.initials: T
authors.lastname: Machemer
authors.forename: Jennifer
authors.initials: J
authors.lastname: Philopena
authors.forename: Murali
authors.initials: M
authors.lastname: Ramachandra
authors.forename: John A
authors.initials: JA
authors.lastname: Howe
authors.forename: Paul
authors.initials: P
authors.lastname: Shabram
authors.forename: Robert
authors.initials: R
authors.lastname: Ralston
authors.forename: Heidrun
authors.initials: H
authors.lastname: Engler
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D016158:Genes, p53; D006801:Humans; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000628:therapy* / Q000821:virology*; D023041:Xenograft Model Antitumor Assays