Transductional Targeting of oncolytic adenoviruses by adapter molecules improves therapy of pSia-expressing tumors by triggering adaptive immune responses

Polysialic acid (polySia) represents an excellent tumor-selective target for oncolytic adenovirus-based therapies since it is selectively expressed on several malignant tumors including small cell lung cancer (SCLC). In this study, we developed a strategy to retarget oncolytic Adenoviruses (OAV) to polySia-expressing tumors using a recombinant bispecific adapter protein. To generate the adapter molecule CARsc-pSia, the soluble CAR ectodomain was fused to a polySia-binding scFv via a fibritin-derived trimerization motif. By infection experiments in cells of defined polySia-status using CARsc-pSia-coated Ad5 parti…