Human leukocyte antigen A*02:01-NY-ESO-1 peptide complex (HLA-A*02:01/NY-ESO-1)

The Human leukocyte antigen A*02:01-NY-ESO-1 peptide complex is a specific peptide-major histocompatibility complex (pMHC) that serves as a critical target for cancer immunotherapy [NIH, Acrobiosystems]. It consists of the HLA-A*02:01 molecule presenting a 9-amino acid peptide, typically SLLMWITQC (residues 157-165), derived from the NY-ESO-1 protein, a well-characterized cancer-testis antigen [NIH]. NY-ESO-1 is highly expressed in various aggressive malignancies, including synovial sarcoma, melanoma, and multiple myeloma, but is absent in normal adult tissues except for the testis, which is an immune-privileged site lacking MHC expression [NIH]. This restricted expression pattern makes the pMHC complex an ideal target for T-cell receptor (TCR) engineered T-cell therapies and TCR-mimetic antibodies, which can recognize intracellularly derived antigens [NIH, Livhospital]. The most prominent therapeutic targeting this complex is afamitresgene autoleucel, which was recently approved for the treatment of synovial sarcoma [FDA]. Clinical use of these therapies requires patient screening for both the HLA-A*02:01 allele and NY-ESO-1 expression in the tumor [NCI]. Potential safety concerns include cytokine release syndrome and neurotoxicity, as well as the theoretical risk of cross-reactivity with similar self-peptides [NIH].

Other names

NY-ESO-1/HLA-A2 complexCTAG1B-HLA-A*02:01 complexNY-ESO-1 peptide-MHC complexSLLMWITQC-HLA-A*02:01 complexNY-ESO-1/HLA-A*02:01

T-cell receptor engineered T-cell (TCR-T) therapies and TCR-mimetic antibodies or bispecific engagers specifically recognize the NY-ESO-1 peptide presented by HLA-A*02:01 on the tumor cell surface, leading to T-cell activation and cytotoxic destruction of the cancer cell [NIH, NCI].