Pharmacologic indicators of antitumor efficacy for oncolytic virotherapy

Cancer Res. 2003 Jul 15;63(14):4003-8.

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.

MeSH terms

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