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Dickkopf-related protein 1 (DKK1) P20 peptide–HLA-A*0201 complex (DKK1 P20–HLA-A*0201)

Target
DKK1 P20–HLA-A*0201
Molecular classification
Peptide-MHC complex, Tumor-associated antigen
01

Overview

The DKK1 P20 peptide–HLA-A*0201 complex is a specific peptide-major histocompatibility complex (pMHC) target used in cancer immunotherapy. It consists of the P20 peptide (sequence: ALGGHPLLGV), a 10-amino acid fragment derived from the Dickkopf-related protein 1 (DKK1), presented on the cell surface by the Human Leukocyte Antigen (HLA) allele A*0201 (Source: NIH, ashpublications.org). DKK1 is a secreted inhibitor of the Wnt signaling pathway that is significantly overexpressed in multiple myeloma and various other cancers, but has very restricted expression in normal adult tissues (Source: NIH, bmj.com). This differential expression makes the DKK1 P20–HLA-A*0201 complex an attractive target for 'TCR-like' monoclonal antibodies and T-cell therapies, which can specifically recognize and eliminate cancer cells while sparing healthy tissue (Source: NIH, Nature Communications). Experimental therapies targeting this complex, including CAR-T cells and TCR-like antibodies, have demonstrated the ability to induce apoptosis and mediate immune-driven cell death in preclinical models of hematologic and solid tumors (Source: NIH, researcher.life). These therapeutic approaches are highly specific to patients carrying the HLA-A*0201 allele, representing a personalized medicine strategy for DKK1-positive malignancies (Source: NIH, haematologica.org).

Other names
DKK1-A2 complexDKK1 P20-HLA-A2 complexDKK1 peptide-MHC complexDKK1 P20-HLA-A*02:01 complexALGGHPLLGV-HLA-A*0201 complex
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Mechanism of action

Recognition of the peptide-MHC complex by TCR-like antibodies or T-cell receptors, leading to targeted lysis of cancer cells via apoptosis, antibody-dependent cellular cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).

03

Biological functions

Antigen presentationImmune responseT-cell activation
04

Disease associations

Multiple myelomaHematological malignancySolid tumorCancer
05

Safety considerations

MHC restriction (limited to HLA-A*0201 positive patients)Potential off-target toxicity if DKK1 is expressed in normal tissuesImmunological escape via HLA downregulation
06

Interacting drugs

DKK1-A2 monoclonal antibody (C2)

2 more in the full profile.

07

Biomarkers

DKK1 expressionHLA-A*0201 genotype

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