Retargeting of oncolytic adenoviruses by bispecific adapter molecules reduces viral liver load and improves therapy by triggering antigen-specific CD8 T-cell responses

Polysialic acid (PolySia) represents an excellent tumor-selective target for oncolytic adenovirus-based therapies since it is selectively expressed on several malignant tumors. In this study, we used a strategy to retarget oncolytic Adenoviruses (OAV) to PolySia-expressing tumors using the bispecific adapter protein CARsc-pSia consisting of the soluble CAR ectodomain and a PolySia-binding scFv domain. By infection experiments in cells of defined PolySia status using CARsc-pSia coated OAV particles, we could show that viral cell entry occurred in a highly PolySia-selective manner. Furthermore, only CARsc-pSia tre…