T-cell receptor (TCR) recognizing cancer-testis antigen-peptide-MHC complex (CTA-specific TCR)

T-cell receptors (TCRs) recognizing cancer-testis antigen (CTA)-derived peptide-MHC complexes represent a specialized class of engineered receptors used in adoptive cell therapies to target intracellular tumor antigens [1]. CTAs, such as NY-ESO-1, MAGE-A4, and PRAME, are ideal therapeutic targets because their expression is typically restricted to immune-privileged germline tissues in healthy adults but becomes aberrantly reactivated in various solid tumors [1]. These TCRs are alpha-beta heterodimers designed to recognize specific peptide fragments presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most commonly HLA-A*02:01 [2, 4]. This mechanism allows TCR-based therapies to target a much broader range of oncogenic proteins compared to CAR-T cells, which are limited to surface-expressed antigens [4]. The most prominent application is TCR-engineered T-cell (TCR-T) therapy, exemplified by the 2024 FDA approval of afamitresgene autoleucel for metastatic synovial sarcoma [2]. Despite their high specificity and potency, these therapies face challenges such as the requirement for specific patient HLA types and the risk of severe off-target toxicities if the TCR cross-reacts with similar peptides in vital organs [3].

Other names

Cancer-testis antigen-specific T-cell receptorNY-ESO-1 TCRMAGE-A4 TCRPRAME TCRCTA-TCRCancer/testis antigen-reactive T-cell receptor

TCR-mediated recognition of intracellularly processed peptide-MHC complexes leading to T-cell activation and targeted tumor cell lysis