461. In Vivo Immunogenicity of Adenoviral Vectors with Improved Dendritic Cell Tropism

Numerous studies have shown that adenovirus (Ad)-mediated delivery of a gene encoding a tumor antigen to dendritic cells (DC) can lead to a T cell response directed against tumor antigens, but the vectors generally used in gene therapy are based on an viral serotype (Ad5) that infects DC very inefficiently. The inefficiency of infection generally requires that cells be manipulated ex vivo, infected, and re-infused. This is complicated, expensive, and involves generation of patient-specific reagents. Ad tropism is largely determined by binding of the viral fiber protein to cells, and DC have been shown to lack the fiber receptor (CAR) used by Ad5. We hypothesized that Ad vectors that more efficiently infected DC would allow vector administration directly to patients and eliminate ex vivo cell culture.