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NY-ESO-1 peptide–HLA class I complex (specifically, NY-ESO-1 (157-165) peptide in complex with HLA-A*02:01) (None universally established; in technical contexts, “NY-ESO-1/HLA-A*02:01 complex” or “NY-ESO-1(157-165)/HLA-A2” may be used.)

Target
None universally established; in technical contexts, “NY-ESO-1/HLA-A*02:01 complex” or “NY-ESO-1(157-165)/HLA-A2” may be used.
Molecular classification
Peptide–MHC complex (pMHC), Immune synapse component, Other (Neoantigen complex, Cancer-testis antigen epitope complex)
01

Overview

The NY-ESO-1 peptide–HLA complex refers to a specific molecular assembly in which a peptide fragment derived from the cancer-testis antigen NY-ESO-1 (typically amino acids 157–165, sequence SLLMWITQC) is bound and presented on the cell surface by the major histocompatibility complex class I molecule HLA-A*02:01. This complex is a well-validated tumor antigen for immunotherapeutic targeting. It is recognized by T cell receptors (TCRs) on cytotoxic CD8+ T cells, facilitating immunologic identification and destruction of cancer cells expressing NY-ESO-1. The complex is a major focus for the development of TCR-T cell therapies and peptide vaccines due to the immunogenicity of NY-ESO-1 and its restricted expression to cancer cells (with negligible expression in normal adult somatic tissues), reducing the risk of off-target effects. Only patients expressing the HLA-A*02:01 allele can present this epitope, which is a critical biomarker for selecting eligible candidates for NY-ESO-1–based therapies. The presence and magnitude of NY-ESO-1-specific T cell responses can serve as biomarkers for therapeutic efficacy and immune monitoring. Safety concerns are primarily related to HLA diversity, tumor escape mechanisms, and the theoretical risk of on-target toxicity if NY-ESO-1 is expressed or re-expressed in normal tissues.

Other names
NY-ESO-1 (157-165) peptide–HLA-A*02:01 complexNY-ESO-1/HLA-A2 complexSLLMWITQC/HLA-A2 (SLLMWITQC is the canonical peptide sequence)NY-ESO-1 pMHC complex (pMHC = peptide–major histocompatibility complex)
02

Mechanism of action

Recognition and binding by cytotoxic CD8+ T cells leading to tumor cell lysis; Stimulation of antigen-specific T cell responses; In TCR-engineered therapies: genetically modified T cells targeting the complex recognize and kill cancer cells presenting NY-ESO-1 peptide via HLA-A2

03

Biological functions

Immune response (T cell-mediated cytotoxicity)Antigen presentationTumor antigen recognition
04

Disease associations

Cancer (notable in melanoma, synovial sarcoma, ovarian cancer, neuroblastoma, multiple solid tumors)
05

Safety considerations

Potential off-tumor/on-target toxicity if NY-ESO-1 or highly similar peptides are aberrantly expressed in normal tissuesHLA restriction limits application only to patients with the HLA-A*02:01 alleleTumor immune escape through HLA loss or antigen downregulation
06

Interacting drugs

Engineered T cell products (TCR-T therapies targeting NY-ESO-1/HLA-A2)

3 more in the full profile.

07

Biomarkers

NY-ESO-1 expression in tumor tissue (for patient selection)HLA-A*02:01 allele status (patients must express this for epitope presentation)NY-ESO-1-specific T cell monitoring (via ELISPOT, tetramer assays, etc.)

Beyond the preview

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