Protein transduction domains fused to CAR ectodomain improve adenoviral infection and enhance oncolysis by tumor specific replicating vectors

Aims: Downregulation of coxsackievirus-adenovirus-receptor (CAR) expression in tumor cells hampers adenoviral cancer gene therapy as infection efficacy is drastically reduced. We demonstrate that adapter proteins comprising the CAR ectodomain fused to protein transduction domains (PTDs) allow efficient adenoviral infection in nonpermissive tumor cells. Methods/Results: Expression vectors for adapter proteins (CARex-PTDs) were generated by fusing the ectodomain of human CAR (CARex) to basically charged PTDs derived from HSV-VP22, HIV-Tat, AntP as well as a repeat of 9 Arginine residues. Treatment of a LacZ transg…