The effectiveness of chimeric antigen receptor T cell (CAR-T) therapy in treating solid tumors is restricted due to factors including antigenic escape and the tumor microenvironment. Although CAR-T cells targeting the NKG2D ligand have shown success in vitro, they have failed to produce complete responses in xenograft solid tumors. To overcome these obstacles, oncolytic viruses have emerged as a potential tool to remodel the tumor microenvironment and induce immunogenic activity to act synergistically with CAR-T therapy.

In this study, we tested whether an oncolytic adenovirus (OAd) armed with IL15, CXCL10, and MICA, a ligand of NKG2D, could improve the outcome of NKG2D CAR-T cell therapy for cancer therapy. We found that MICA was expressed in tumoural cell lines 72 hours after armed OAd infection, and the tumor cells secreted IL15 and CXCL10. Additionally, armed OAd induced oncolysis in these tumor cell lines and enhanced CAR-T cell activation and cytotoxicity, resulting in improved antitumor efficacy compared to monotherapies. The combination approach also allow CAR-T cell infiltration in mouse xenograft models.

Overall, the study suggests that combining oncolytic viruses with CAR-T cells could be a promising approach to overcome the challenges of CAR-T cell therapy in solid tumors. Further clinical trials are needed to evaluate this combination approach.