CELL INTELLIGENCE · 肿瘤细胞治疗研究

T cells engineered to express chimeric antigen receptors (CARs) are a promising modality to treat refractory cancers. CD19 CAR-T therapy has achieved remarkable responses in against B-cell lymphomas, however, challenges persist for acute myeloid leukemia (AML) and solid malignancies. B7H3 is an immune regulatory molecule that is highly expressed in various tumor cells. Its abnormal expression in acute AML and esophageal squamous cell carcinoma (ESCC) is closely related to tumor progression. Here, we describe B7H3-targeted CAR-T cells constructed using the single-chain variable fragment (scFv) of an anti-B7H3 antibody and systematically evaluated their safety and efficacy in vitro and in mice models of AML and ESCC. Based on the monoclonal antibody targeting B7H3, namely A172 which screened according to phage antibody display library technology, we undertook humanization of the A172 antibody, resulting in A172-hu4, and further verified its affinity and cytotoxicity in the cell lines of AML and ESCC. The resulting A172-hu4-CAR-T displayed strong IFN- and IL-2 production and cytotoxic effects in vitro. We also identify that A172-hu4-CAR-T treatment could lead to more pronounced tumor suppression in AML and ESCC xenograft mouse models with no obvious toxic reactions to mice main organs. Accordingly, this study provides a novel target for CAR-T therapy in AML and ESCC to promote the development of clinical treatment strategies.