Target intelligence / Profile preview

p53 peptide–HLA-A*0201 complex

Molecular classification
Peptide–MHC class I complex (other), Tumor antigen–MHC class I complex, Immune recognition molecule (other)
01

Overview

The p53 peptide/HLA-A*0201 complex is a peptide-major histocompatibility complex formed when a nine-amino-acid peptide from the tumor suppressor protein p53 is presented by the HLA-A*0201 MHC class I molecule on the surface of cells. In cancer, p53 is often mutated or stabilized, resulting in increased intracellular levels and enhanced peptide presentation. This complex is recognized by cytotoxic T cells and is a validated immunological target for TCR-based and TCR-mimetic immunotherapies, due to its specific expression on a wide range of tumor cells but limited display on normal tissue, thereby enabling selective targeting of malignant cells in HLA-A*0201-positive patients[1][4].

Other names
p53/HLA-A2 complexp53-derived peptide–HLA-A*0201 complexp53 peptide–MHC class I (HLA-A2) complexTumor-associated p53 peptide–MHC complex
02

Mechanism of action

TCR mimetic antibodies or engineered T cells recognize the p53-derived peptide presented by HLA-A*0201, binding specifically to tumor cells overexpressing or abnormally presenting p53 antigens, thereby inducing targeted cytotoxicity[1][4]. These therapies leverage the differential presentation of p53 peptides in cancer versus normal tissues to selectively target tumor cells[1].

03

Biological functions

Immune recognitionAntigen presentationTumor immune surveillanceActivation of cytotoxic T lymphocytes (CTLs)
04

Disease associations

Cancer (various solid tumors and hematologic malignancies)Other (potentially any context where p53 peptides are abnormally presented, but primary focus is cancer)
05

Safety considerations

Risk of off-tumor targeting if non-tumor cells present similar p53 peptides in the context of HLA-A*0201[1][4]Tumor immune escape by antigen loss or HLA downregulationLimited patient population to HLA-A*0201-positive individuals (prevalence varies by ethnic background)
06

Interacting drugs

TCR-mimic (TCRm) antibodies (e.g., T1-116C)

2 more in the full profile.

07

Biomarkers

Presence of HLA-A*0201 alleleAccumulation of p53 protein (by immunohistochemistry or sequencing for TP53 mutations)Presentation of p53 peptides on tumor cell surface (can be surmised from tumor status, though direct detection may be challenging)

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