CD276 and neoplasm: Like TCEs, CAR-T therapy faces challenges in solid tumors due to multiple reasons: tumor antigen heterogeneity and escape, toxicity, inefficient tumor infiltration, poor persistency, and immunosuppressive TME.1048 Next-generation CAR-T cells for overcoming those challenges are under extensive investigations.1049,1050 For instance, to avoid tumor-antigen escape as well as off-target toxicity, dual CARs are designed to co-targeting two different tumor antigens, such as CD19/CD22, CD19/CD22, GD2/CD70, GD2/PSMA, EGFR/B7H3, etc. (Table 5).