Disease-associated cell-surface antigen

Disease-associated cell-surface antigens recognized by the encoded CAR refers to the broad class of molecular markers expressed on the exterior of pathological cells that serve as the binding targets for Chimeric Antigen Receptor (CAR) therapies (June et al., 2018). These antigens are typically proteins or glycoproteins that are either uniquely expressed on diseased cells or significantly overexpressed compared to healthy tissues, allowing engineered immune cells to distinguish between them (Miliotou & Papadopoulou, 2018). The encoded CAR is a synthetic fusion protein that combines an extracellular antigen-recognition domain with intracellular T-cell signaling domains (Labanieh et al., 2018). Upon binding to the target antigen, the CAR-T cell is activated to perform direct cytotoxic killing of the disease-associated cell, a process that occurs independently of Major Histocompatibility Complex (MHC) presentation (Neelapu et al., 2018). This approach has been most successful in hematologic malignancies targeting antigens like CD19 and BCMA, though research into solid tumor antigens continues (FDA, 2024). The selection of an appropriate antigen is the most critical factor in CAR design to ensure high therapeutic efficacy while minimizing on-target, off-tumor toxicities (Hay et al., 2017).

Other names

Tumor-associated antigen (TAA)Tumor-specific antigen (TSA)CAR-T targetSurface-expressed disease marker

Chimeric Antigen Receptors (CARs) recognize disease-associated cell-surface antigens via an extracellular antigen-binding domain (typically a single-chain variable fragment), which triggers T-cell activation and cytotoxic activity through intracellular signaling domains such as CD3-zeta and costimulatory molecules like 4-1BB or CD28, bypassing the need for Major Histocompatibility Complex (MHC) presentation (June et al., 2018; Miliotou & Papadopoulou, 2018).