Development of chimeric antigen receptor (CAR)-T cells targeting A56 viral protein implanted by oncolytic virus

To address the challenge of solid tumor targeting in CAR -T therapy, we utilized the A56 antigen, which is uniquely expressed on a diverse range of cancer cells following the systemic administration of an oncolytic vaccinia virus (OVV). Immunohistochemical assays precisely confirmed exclusive localization of A56 to tumor tissues. In vitro studies demonstrated a distinct superiority of A56 -dependent CAR -T cytotoxicity across multiple cancer cell lines. Building on these in vitro observations, we strategically administered A56 CAR -T cells, OVV, and hydroxyurea (HU) combination in HCT-116 tumor -bearing non -obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, leading to a significant reduction in tumor size and an extended time to progression. Consequently, A56 -targeting combinatorial immunotherapy provides the benefit of reducing inadvertent CAR -T effects on normal cells while preserving its effectiveness against cancer cells. Furthermore, our approach of implanting A56 via OVV on tumors facilitates a wide therapeutic application of CAR -T cells across various solid tumors.