Pharmacologic indicators of antitumor efficacy for oncolytic virotherapy.
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.
Demers
G William
GW
Canji, Inc., San Diego, California 92121, USA. bill.demers@canji.com
Johnson
Duane E
DE
Tsai
Van
V
Wen
Shu-Fen
SF
Quijano
Erlinda
E
Machemer
Todd
T
Philopena
Jennifer
J
Ramachandra
Murali
M
Howe
John A
JA
Shabram
Paul
P
Ralston
Robert
R
Engler
Heidrun
H
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