T cell receptor–NY-ESO-1 peptide–MHC complex (TCR–NY-ESO-1–MHC)

The T cell receptor–NY-ESO-1 peptide–MHC complex is a molecular assembly essential for the cellular immune system to identify and eliminate malignant cells. NY-ESO-1, encoded by the CTAG1B gene, is a cancer-testis antigen that is typically expressed only in the testis and placenta but becomes aberrantly upregulated in various cancers, including synovial sarcoma and melanoma [1]. The target complex forms when an 8-11 amino acid peptide derived from NY-ESO-1 (most commonly the SLLMWITQC decamer) is processed and presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, specifically HLA-A*02:01 [2]. Therapeutic strategies targeting this complex involve engineering T cells with high-affinity T cell receptors (TCR-T) or using soluble bispecific TCR molecules to bridge T cells to the tumor cells [3]. These therapies, such as the recently FDA-approved afamitresgene autoleucel, have demonstrated the ability to induce durable clinical responses in patients with advanced solid tumors [4]. However, the efficacy of these treatments is strictly limited to patients who are HLA-A*02:01 positive and whose tumors express the NY-ESO-1 antigen [5]. Citations: [1] Thomas, R. et al. (2018). Frontiers in Immunology. [2] UniProt KB - P78358 (CTAG1B_HUMAN). [3] Adaptimmune Therapeutics. (2024). Tecelra Prescribing Information. [4] FDA. (2024). FDA approves first gene therapy to treat synovial sarcoma. [5] D'Angelo, S. P. et al. (2018). Cancer Discovery.

Other names

NY-ESO-1/HLA-A*02:01 complexNY-ESO-1–specific TCR–pMHCCTAG1B–HLA complexNY-ESO-1 peptide-MHCTCR-pMHC (NY-ESO-1)

TCR-mediated recognition of the NY-ESO-1 peptide-MHC complex leading to T-cell activation and targeted tumor cell lysis.