NY-ESO-1 peptide–MHC class I complex

The **NY-ESO-1 peptide–MHC class I complex** refers to a complex formed between a short peptide derived from the cancer/testis antigen NY-ESO-1 (typically residues 157–165, SLLMWITQC) and the human leukocyte antigen (HLA) class I molecule, most commonly HLA-A*02:01. This complex is presented by the surface of tumor cells expressing NY-ESO-1 and is recognized by cytotoxic T lymphocytes, making it a highly immunogenic target for cancer immunotherapy. NY-ESO-1 is normally restricted to germ cells but is aberrantly expressed in many tumors, contributing to its attractiveness as a tumor-associated antigen. The NY-ESO-1 peptide–MHC class I complex is targeted by a variety of therapeutic approaches, including peptide vaccines, TCR gene therapies, and bispecific antibodies, with the aim of inducing an antitumor immune response by activating NY-ESO-1–specific T cells[1][3][4][5][6][7]. The structure and immunogenicity of this complex have been extensively studied, and its specificity and interaction with TCRs and engineered antibodies have informed the rational development of targeted cancer immunotherapies[1][3][6][7]. Biomarker strategies typically include tumor NY-ESO-1 expression and the patient's HLA type (essential for therapy eligibility). Safety concerns revolve mainly around the possibility of off-tumor effects in nonmalignant tissues expressing NY-ESO-1, although this is rare due to its restricted normal expression pattern.

Other names

NY-ESO-1–HLA-A2 complexNY-ESO-1 (157–165) peptide–HLA-A*02:01 complexNY-ESO-1 pMHC complexSLLMWITQC–MHC I complex

Immune recognition and killing of NY-ESO-1–expressing tumor cells via cytotoxic T lymphocytes recognizing the presented peptide TCR-mimic antibody recognition and redirection of immune effectors via engineered biologics or cell therapies