Other Chimeric Antigen Receptor Antigens (Other CAR Antigens)

The term 'Other CAR antigens' serves as a collective category for a diverse array of molecular targets utilized in Chimeric Antigen Receptor (CAR) T-cell therapies that are distinct from the primary clinical targets CD19 and B-cell maturation antigen (BCMA). These antigens include a variety of surface-expressed proteins, glycoproteins, and glycolipids that are overexpressed or mutated in malignant cells, such as CD20, CD22, and CD123 for hematologic cancers, and Mesothelin, GD2, HER2, and Claudin 18.2 for solid tumors (Chen et al., Journal of Hematology & Oncology, 2023). The biological function of these targets varies widely, ranging from cell adhesion and signaling to metabolic regulation, but their primary utility in therapy is to serve as a docking site for engineered immune cells to initiate a targeted cytotoxic response (NIH/National Cancer Institute). While expanding the repertoire of CAR antigens is essential for treating a broader range of cancers and overcoming resistance to first-generation CAR-T therapies, many of these 'other' antigens are also expressed at low levels on vital healthy tissues. This shared expression presents a significant therapeutic challenge, as it increases the risk of 'on-target, off-tumor' toxicities, necessitating the development of more precise gating strategies, such as logic-gated CARs or transiently active mRNA CARs, to improve safety profiles in clinical settings (Labanieh & Mackall, Nature Reviews Clinical Oncology, 2023).

Other names

Miscellaneous CAR-T targetsNon-canonical CAR antigensSolid tumor CAR targetsAlternative CAR-T cell targets

Chimeric Antigen Receptor (CAR) T-cells are engineered to express a synthetic receptor consisting of an extracellular antigen-binding domain (usually a single-chain variable fragment, scFv) linked to intracellular signaling domains (e.g., CD3-zeta and costimulatory domains like 4-1BB or CD28). Upon binding to the specific 'other' antigen on the target cell surface, the CAR-T cell is activated, leading to cytokine release, proliferation, and direct cytotoxic lysis of the target cell (Labanieh & Mackall, Nature Reviews Clinical Oncology, 2023).