New York esophageal squamous cell carcinoma 1 (NY-ESO-1) peptide-Major Histocompatibility Complex (MHC) (NY-ESO-1 pMHC)

New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a well-known cancer-testis antigen (CTA) encoded by the CTAG1B gene [UniProt, 2024]. In healthy individuals, its expression is restricted to the germ cells of the testis and placenta; however, these tissues do not express Major Histocompatibility Complex (MHC) class I molecules, effectively shielding them from T-cell recognition [PubMed, 2021]. In many cancers, such as synovial sarcoma and melanoma, NY-ESO-1 is aberrantly expressed, and its intracellular proteins are degraded into peptides that are presented on the cell surface by MHC molecules, most commonly HLA-A*02:01 [NIH, 2023]. These peptide-MHC (pMHC) complexes serve as the specific target for advanced immunotherapies, including T-cell receptor (TCR) engineered T-cells and bispecific T-cell engagers [PubMed, 2022]. For instance, afamitresgene autoleucel is an FDA-approved TCR-T cell therapy designed to recognize the NY-ESO-1 pMHC complex on tumor cells, leading to targeted cell lysis [FDA, 2024]. Because of the restricted expression of NY-ESO-1 in normal tissues, these pMHC complexes are considered highly attractive targets with a favorable safety profile regarding off-tumor toxicity [PubMed, 2023]. The specificity of the pMHC complex allows for potent anti-tumor activity while minimizing damage to normal somatic tissues.

Other names

CTAG1B peptide-MHC complexNY-ESO-1/HLA-A*02:01 complexCancer/testis antigen 1B peptide-MHCNY-ESO-1-derived peptide-MHC

T-cell receptor (TCR) binding to the peptide-MHC complex, triggering T-cell activation, cytokine release, and direct cytotoxic lysis of the target cell.