MHC class I molecules presenting NY-ESO-1 tumor antigen peptides (NY-ESO-1/HLA-A2 complex)

MHC class I molecules presenting NY-ESO-1 tumor antigen peptides represent a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy [1.4.5]. NY-ESO-1, encoded by the CTAG1B gene, is a cancer-testis antigen that is typically expressed only in the testis and placenta but is highly upregulated in various cancers, such as synovial sarcoma, melanoma, and multiple myeloma [1.1.2, 1.4.1]. The most common epitope targeted is the SLLMWITQC peptide presented by the HLA-A*02:01 allele [1.4.1, 1.4.2]. This complex is recognized by the T-cell receptor (TCR) of cytotoxic T lymphocytes, making it a primary target for TCR-engineered T-cell (TCR-T) therapies and TCR-like antibodies [1.3.1, 1.3.3]. Unlike CAR-T cells that target surface proteins, TCR-T cells can recognize intracellular antigens processed and presented as peptides on the cell surface [1.3.1]. Drugs like afamitresgene autoleucel (Tecelra) and letetresgene autoleucel have been developed to target this complex, showing significant clinical efficacy in treating advanced solid tumors [1.2.1, 1.3.2]. Safety considerations include potential cytokine release syndrome (CRS) and the risk of antigen escape through MHC downregulation or loss of heterozygosity [1.1.2, 1.1.5].

Other names

NY-ESO-1/HLA-A*02:01 complexNY-ESO-1 peptide-MHC complexHLA-A*02:01-restricted NY-ESO-1 epitopeSLLMWITQC-HLA-A*02:01 complexNY-ESO-1/HLA-A2 complexNY-ESO-1/MHC-I complex

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and tumor cell lysis [1.3.1, 1.3.5].