Tumor-associated antigen-specific T-cell receptor (TAA-specific TCR)

Tumor-associated antigen-specific T-cell receptors (TAA-specific TCRs) are engineered or naturally occurring heterodimeric surface receptors that enable T lymphocytes to recognize specific peptide fragments presented by major histocompatibility complex (MHC) molecules (Nature Reviews Clinical Oncology, 2021). Unlike chimeric antigen receptors (CARs) which are limited to surface-bound proteins, TAA-specific TCRs can target intracellular proteins, which constitute the majority of potential tumor antigens (Journal of Hematology & Oncology, 2022). These receptors are central to TCR-engineered T-cell (TCR-T) therapies, where autologous T cells are modified to express a high-affinity TCR targeting antigens such as MAGE-A4 or NY-ESO-1 (The Lancet, 2024). Additionally, soluble TCR-based bispecific molecules, such as ImmTACs, utilize these receptors to redirect the endogenous immune system toward malignant cells (New England Journal of Medicine, 2021). The clinical utility of TAA-specific TCRs is highly dependent on the patient's human leukocyte antigen (HLA) type, as the TCR must match the specific MHC allele presenting the antigen (Nature Reviews Drug Discovery, 2023). While highly effective in certain solid tumors like synovial sarcoma and uveal melanoma, challenges include potential on-target off-tumor toxicities and the risk of cytokine release syndrome (The Lancet, 2024).

Other names

Tumor-specific T-cell receptorAntigen-specific TCRTAA-TCREngineered T-cell receptorTCR-T target

Engineered T-cell therapy (TCR-T) involves the ex vivo modification of autologous T cells to express a specific TCR alpha/beta heterodimer that recognizes a tumor-associated antigen (TAA) peptide presented by a specific major histocompatibility complex (MHC) molecule, triggering T-cell activation and targeted cytotoxicity (Nature Reviews Clinical Oncology, 2021).