Cancer-testis antigen 1B-derived peptide–MHC complex (NY-ESO-1 pMHC)

NY-ESO-1 (New York esophageal squamous cell carcinoma 1), encoded by the CTAG1B gene, is a prominent member of the cancer-testis antigen (CTA) family. It is characterized by high expression in various malignancies—such as synovial sarcoma, melanoma, and multiple myeloma—while remaining epigenetically silenced in normal adult somatic tissues, except for the germ cells of the testis and placenta (UniProt P78358). Because germ cells do not express HLA molecules, NY-ESO-1 is a highly specific target for T-cell-based therapies. The target specifically refers to the processed NY-ESO-1 peptide (most commonly the 157-165 decamer SLLMWITQC) presented on the cell surface by Major Histocompatibility Complex (MHC) Class I molecules, typically HLA-A*02:01 (PubMed: 32661138). Therapeutic interventions, such as TCR-engineered T cells (TCR-T) like afamitresgene autoleucel, utilize high-affinity T-cell receptors to recognize this complex, triggering a potent cytotoxic immune response against the tumor (FDA: Tecelra Approval 2024). This approach bypasses the need for surface protein expression, allowing the immune system to target intracellular oncogenic proteins that are otherwise inaccessible to standard monoclonal antibodies (PubMed: 25605916).

Other names

NY-ESO-1 peptide-MHC complexCTAG1B peptide-HLA complexLAGE-2 peptide-MHC complexCancer/testis antigen 1CT6.1

T-cell receptor (TCR) mediated recognition of the specific NY-ESO-1 peptide presented by MHC Class I molecules (typically HLA-A*02:01), leading to T-cell activation, cytokine release, and direct cytotoxic lysis of tumor cells.