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NY-ESO-1 peptide–HLA-A*0201 complex (NY-ESO-1/HLA-A*0201 complex)

Target
NY-ESO-1/HLA-A*0201 complex
Molecular classification
Other (peptide–MHC complex; not a conventional receptor, enzyme, or transporter, but functions as an immunological target structure)
01

Overview

The NY-ESO-1 peptide–HLA-A*0201 complex is a tumor-associated antigenic target composed of the cancer/testis antigen NY-ESO-1 presented as a peptide (commonly residues 157–165, e.g., SLLMWITQC) bound in the groove of the class I MHC molecule HLA-A*0201. This peptide–MHC (pMHC) complex is recognized by specific cytotoxic T lymphocytes (CD8+ T cells) and is a validated target in cancer immunotherapy, notably for adoptive TCR-transduced T cell therapies, bispecific T cell engagers, and TCR-mimic antibodies. The complex is not a canonical receptor or enzyme but rather a composite molecular target that mediates tumor cell recognition and destruction by engineered immune effectors or through vaccination approaches. Its unique immunogenicity and restricted expression profile in tumors versus normal tissues make it a leading model antigen for cancer immunotherapies[3][4][5][1][2].

Other names
NY-ESO-1–HLA-A2 complexHLA-A*02:01/NY-ESO-1 complexNY-ESO-1/HLA-A2 complexNY-ESO-1:HLA-A*0201 peptide–MHC complex
02

Mechanism of action

Recognition of NY-ESO-1 peptide presented by HLA-A*0201 on tumor cells triggers binding by engineered TCRs or TCR-mimic antibodies, resulting in targeted cytotoxicity or immune activation[1][4][5]. Some bispecific T cell engagers are designed to redirect T cells specifically to NY-ESO-1/HLA-A*0201-expressing cells[2].

03

Biological functions

Immune response (serves as the antigenic complex presented by tumor or antigen-presenting cells and recognized by T cell receptors (TCRs), thus mediating cytotoxic immune targeting)Other (serves as a molecular scaffold for therapeutic TCRs and TCR-like antibodies)
04

Disease associations

Cancer (specifically various solid tumors and sarcomas that aberrantly express NY-ESO-1)Other (serves as a diagnostic and immunotherapeutic marker in cancer)
05

Safety considerations

Off-target toxicity if TCRs or TCR-like antibodies cross-react with similar self-peptide/HLA complexes[5].Limitations to HLA-A*0201–positive patients, restricting therapy population[5].Potential for on-target, off-tumor effects if NY-ESO-1 is re-expressed in non-tumor tissues (rare, as NY-ESO-1 is mostly tumor/testis restricted)[5][3].
06

Interacting drugs

Engineered TCR-T cell products specific for NY-ESO-1/HLA-A*0201

2 more in the full profile.

07

Biomarkers

Presence of NY-ESO-1 expression in tumors (detected by RT-PCR, IHC, etc.)HLA-A*0201 expression (by HLA typing techniques)Circulating NY-ESO-1–specific T cells in blood can be monitored to track immune responses[3][5].

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