New York esophageal squamous cell carcinoma 1 peptide-major histocompatibility complex (NY-ESO-1-pMHC) (NY-ESO-1-pMHC)

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a well-characterized cancer-testis antigen (CTA) encoded by the CTAG1B gene (UniProt: P12101). Under normal physiological conditions, its expression is restricted to the germ cells of the testis and placental trophoblasts, which lack MHC class I expression, making it an ideal target for immunotherapy (PubMed: 32661138). In various malignancies, NY-ESO-1 is aberrantly re-expressed and processed into intracellular peptides that are presented on the cell surface by Major Histocompatibility Complex (MHC) molecules, most notably HLA-A*02:01. These peptide-MHC (pMHC) complexes are recognized by the T-cell receptors (TCRs) of cytotoxic T lymphocytes, triggering a targeted immune response against the tumor. Therapeutic strategies targeting NY-ESO-1 pMHC complexes include TCR-engineered T-cell (TCR-T) therapies, such as the FDA-approved afamitresgene autoleucel, as well as bispecific T-cell engagers and cancer vaccines (FDA: Afami-cel). These treatments aim to harness the immune system to selectively eliminate NY-ESO-1-positive cancer cells while sparing healthy tissues, although challenges such as antigen escape and cytokine release syndrome remain (ClinicalTrials.gov: NCT04044859).

Other names

CTAG1B-pMHCCancer/testis antigen 1B peptide-MHC complexNY-ESO-1/HLA-A*02:01 complexLAGE-2-pMHCNY-ESO-1 epitope-MHC complex

Drugs targeting this complex typically utilize engineered T-cell receptors (TCR-T) or bispecific molecules to recognize the specific peptide-MHC epitope on the tumor cell surface, leading to T-cell mediated cytotoxicity (PubMed: 32661138, FDA: Afami-cel).