Major Histocompatibility Complex-NY-ESO-1 peptide complex (MHC-NY-ESO-1)

The Major Histocompatibility Complex (MHC) molecules presenting NY-ESO-1 peptides represent a specialized therapeutic target for cancer immunotherapy (Source: PubMed 9050851). NY-ESO-1, a cancer-testis antigen encoded by the CTAG1B gene, is expressed in various malignancies such as synovial sarcoma and melanoma but is restricted to germ cells in healthy adults (Source: UniProt P78358). Intracellular NY-ESO-1 is processed into peptides, most notably the SLLMWITQC epitope, which are presented on the cell surface by MHC Class I molecules, predominantly HLA-A*02:01 (Source: PubMed 10630597). This peptide-MHC (pMHC) complex is the specific ligand for engineered T-cell receptors (TCRs) used in TCR-T cell therapies and bispecific TCR molecules (Source: PubMed 29533921). These therapies, such as letetresgene autoleucel, redirect the patient's immune system to recognize and destroy tumor cells expressing the complex (Source: ClinicalTrials.gov NCT03645928). The high specificity of this target minimizes off-tumor toxicity, although challenges such as cytokine release syndrome and HLA downregulation remain significant considerations in clinical development.

Other names

HLA-A*02:01/NY-ESO-1 complexNY-ESO-1/HLA complexCTAG1B-HLA complexpMHC complexNY-ESO-1 peptide-MHC complex

Engineered T-cell receptor (TCR) binding to the peptide-MHC complex, triggering T-cell activation, cytokine release, and cytotoxic granzyme/perforin-mediated lysis of the target cell (Source: PubMed 29533921).