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

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 Ads-immune patients. We studied the safety and efficacy of rare serotypes AM, 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, Ads was often more active than AM, among CD46-binding viruses Ad35 was generally more cytotoxic than Ad11 in cell culture studies. Ads, Ad6, and Ad11 demonstrated similar anticancer activity in vivo, whereas Ad35 was not efficacious. Hepatotoxicity developed only in Ads-injected mice. Predosing with Ad11 and Ad35 did not increase infection of hepatocytes with Ads-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. (C) 2009 Elsevier Inc. All rights reserved.