T-cell associated antigens

T-cell associated antigens are a broad category of cell surface proteins expressed on T lymphocytes that mediate critical immune functions, including antigen recognition, signal transduction, and cellular adhesion (1.1.1, 1.4.3). This group encompasses pan-T-cell markers such as CD2, CD3, CD5, and CD7, as well as subset-specific glycoproteins like CD4 and CD8, and regulatory molecules including immune checkpoints (e.g., PD-1, CTLA-4) and costimulatory receptors (e.g., CD28, 4-1BB) (1.2.1, 1.2.4). These antigens facilitate the interaction between T cells and antigen-presenting cells or target cells, ensuring a coordinated immune response (1.4.1). In clinical pathology, the aberrant expression or loss of these lineage-specific antigens is a hallmark of T-cell malignancies, such as peripheral T-cell lymphoma (PTCL) and T-cell acute lymphoblastic leukemia (T-ALL) (1.2.2, 1.4.2). Therapeutically, these antigens are exploited as targets for monoclonal antibodies, antibody-drug conjugates (ADCs), and bispecific T-cell engagers (BiTEs) to treat cancers and autoimmune disorders (1.2.1, 1.2.4). For example, alemtuzumab targets CD52 to deplete malignant lymphocytes, while blinatumomab and other bispecifics target CD3 to redirect T-cell cytotoxicity toward tumor cells (1.2.1, 1.2.4). Additionally, checkpoint inhibitors targeting PD-1 or CTLA-4 have revolutionized the treatment of various cancers by enhancing T-cell activity (1.2.4). However, targeting these antigens involves significant challenges, including the risk of "fratricide" in CAR-T cell therapy, where the therapeutic cells target each other, and systemic toxicities such as cytokine release syndrome (CRS) or profound lymphopenia (1.2.3).

Other names

T-cell markersT-cell surface antigensT-cell lineage antigensT-cell differentiation antigensT-cell surface glycoproteins

Drugs targeting T-cell associated antigens function through several mechanisms: direct depletion of malignant cells via antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC), delivery of cytotoxic payloads via antibody-drug conjugates (ADCs), redirection of T-cell cytotoxicity via bispecific antibodies, and modulation of immune checkpoints to enhance anti-tumor responses.