Modified adenovirus induces antigen specific T cells and effector memory T cells in mice

Abstract

Abstract We engineered a novel adenovirus with a modified capsid for use as an integrated anticancer gene therapy and to circumvent pre-existing adenovirus immunity. The modified adenovirus, SynBAd, when administered intravenously, induced antigen-specific CD8 T cell immunity in the liver of mice (C57BL/6) and a splenic population of effector memory T cells at levels equivalent with those induced by human Adenovirus serotype 5 (Ad5). Although the virus elicited equivalent liver and splenic T cell responses, SynBAd did not elevate liver enzymes as commonly seen with Ad5. SynBAd bound factor X with similar affinity to Ad5, though it localized preferentially to the spleen relative to Ad5, suggesting greater systemic immune stimulation. CD8 T cells in the liver and spleen increased with SynBAd administration, indicating that the virus acts as a potent mobilizer of T cells. Although SynBAd is a potent immunogen, antibodies generated in mice immunized with Ad5 only weakly neutralized SynBAd infection in vitro, suggesting that preexisting Ad5 antibodies will not dramatically influence SynBAd efficacy. Localization of the adenovirus after administration, activation of antigen specific T cells, and mobilization of effector memory T cells, suggest that this approach will promote an antitumor immune response that could be used in multiple tumor indications.