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

Peter A. Sieling, Justin Golovato, Stephen Benz, Kayvan R. Niazi, Shahrooz Rabizadeh Sagittarius Bio, Inc.

We engineered a modified adenovirus to express a novel antigen for use as a therapeutic cancer vaccine and circumvent pre-existing adenovirus immunity. The modified adenovirus, SynBAd, when administered intravenously, induced antigen-specific CD8 T cell immunity in mice (C57BL/6) and a population of effector memory T cells at levels equivalent with those induced by human Adenovirus serotype 5 (Ad5). The virus predominantly localized to the liver and spleen, suggesting 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 vaccine after administration, activation of antigen specific T cells, and mobilization of effector memory T cells, suggest that this vaccine approach will promote a tumor controlling immune response that could be used in multiple tumor indications.