Tumor antigen recognized by the CAR (CAR-Ag)

A tumor antigen recognized by the CAR refers to a specific molecular entity, typically a cell-surface protein, carbohydrate, or glycolipid, that serves as the target for Chimeric Antigen Receptor (CAR) T-cell therapy [1.2.1]. These antigens are ideally expressed at high levels on malignant cells and at minimal or no levels on vital healthy tissues to ensure therapeutic efficacy and safety [1.2.2]. Common examples of such antigens include CD19 for B-cell malignancies and B-cell maturation antigen (BCMA) for multiple myeloma [1.2.1]. Upon binding to the antigen, the CAR-T cell is activated, leading to the release of cytotoxic granules (perforin and granzymes) and inflammatory cytokines that mediate tumor cell destruction [1.3.2]. The interaction is MHC-independent, allowing CAR-T cells to recognize antigens that are not presented by the major histocompatibility complex [1.2.1]. However, the clinical success of targeting these antigens can be limited by 'antigen escape,' where tumor cells downregulate the target antigen to evade immune detection [1.2.3]. Identifying novel, highly specific antigens remains a significant challenge, particularly for solid tumors where targetable antigens are often shared with normal tissues [1.2.2]. Safety concerns such as on-target off-tumor toxicity arise when the CAR recognizes the target antigen on non-malignant cells [1.2.2]. Monitoring antigen expression levels is crucial for patient selection and for assessing the risk of relapse [1.2.3]. Future strategies involve multi-antigen targeting to overcome heterogeneity and improve the durability of responses [1.2.2].

Other names

Tumor-associated antigenTumor-specific antigenCAR-T targetChimeric antigen receptor targetTAATSA

Binding of the CAR's extracellular antigen-recognition domain to the tumor antigen triggers intracellular signaling through CD3-zeta and costimulatory domains, leading to T-cell activation and tumor cell lysis.