Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents

Elena V. Shashkova, Shannon M. May, Michael A. Barry

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Human adenovirus type 5 (Ad5) has been the most popular platform for the development of oncolytic Ads. Alternative Ad serotypes with low seroprevalence might allow for improved anticancer efficacy in Ad5-immune patients. We studied the safety and efficacy of rare serotypes Ad6, Ad11 and Ad35. In vitro cytotoxicity of the Ads correlated with expression of CAR and CD46 in most but not all cell lines. Among CAR-binding viruses, Ad5 was often more active than Ad6, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ad5, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ad5-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ad5-based vector demonstrating different interaction of these Ads with Kupffer cells. Data obtained in this study suggest developing Ad6 and Ad11 as alternative Ads for anticancer treatment.

Original languageEnglish (US)
Pages (from-to)311-320
Number of pages10
JournalVirology
Volume394
Issue number2
DOIs
StatePublished - Nov 25 2009

Keywords

  • Adenovirus
  • Kupffer cells
  • Oncolytic viruses
  • Toxicity
  • Xenograft model antitumor assays

ASJC Scopus subject areas

  • Virology

Fingerprint Dive into the research topics of 'Characterization of human adenovirus serotypes 5, 6, 11, and 35 as anticancer agents'. Together they form a unique fingerprint.

Cite this