T-cell redirecting targets

T-cell redirecting targets are a broad class of cell-surface proteins utilized in cancer immunotherapy to facilitate the direct interaction between cytotoxic T cells and malignant cells (Labrijn et al., 2019, Nature Reviews Drug Discovery). These targets are typically tumor-associated antigens (TAAs) such as CD19, CD20, or B-cell maturation antigen (BCMA), which are paired with the CD3 epsilon subunit of the T-cell receptor (TCR) complex via bispecific antibodies or chimeric antigen receptors (CARs) (Goebeler & Bargou, 2020, Nature Reviews Clinical Oncology). By physically bridging the T cell and the target cell, these therapies bypass the requirement for major histocompatibility complex (MHC) class I presentation, allowing for potent, antigen-specific lysis of tumor cells (Einsele et al., 2020, Cancer). This mechanism of action has revolutionized the treatment of hematologic malignancies, though it is associated with unique toxicities like cytokine release syndrome (CRS) and neurotoxicity (Shimasaki et al., 2020, Nature Reviews Drug Discovery). Ongoing research aims to expand these targets to solid tumors and autoimmune diseases by identifying antigens with high tumor specificity to minimize on-target off-tumor effects (Middenti et al., 2022, Frontiers in Immunology). Clinically validated targets in this category include CD19 for B-cell acute lymphoblastic leukemia and BCMA for multiple myeloma (FDA, 2023, Blincyto and Tecvayli Prescribing Information).

Other names

T-cell engager targetsBispecific T-cell engager targetsRedirected T-cell therapy targetsTumor-associated antigens for T-cell redirection

Simultaneous binding of a tumor-associated antigen on a target cell and the CD3 epsilon subunit of the T-cell receptor complex on a T cell, leading to MHC-independent T-cell activation, cytokine release, and perforin/granzyme-mediated lysis of the target cell (Labrijn et al., 2019, Nature Reviews Drug Discovery).