Dickkopf-related protein 1 peptide P20 presented by HLA-A*0201 (DKK1-P20/HLA-A*0201)

The Dickkopf-related protein 1 (DKK1) peptide P20 presented by HLA-A*0201 is a specific peptide-major histocompatibility complex (pMHC) target utilized in advanced cancer immunotherapy. DKK1 is a secreted glycoprotein that acts as a high-affinity antagonist of the Wnt/beta-catenin signaling pathway, playing a critical role in bone homeostasis and cellular proliferation (Source: UniProt P57088). While its expression is restricted in healthy adults, DKK1 is significantly overexpressed in various malignancies, particularly multiple myeloma and prostate cancer, where it contributes to osteolytic bone lesions and tumor progression (Source: PubMed 22302738). The P20 epitope, consisting of the amino acid sequence ALMSHGLIC (residues 20-28), is derived from the DKK1 signal peptide and is efficiently processed and presented by the HLA-A*0201 allele on the surface of cancer cells (Source: Blood, Qian et al., 2012). This pMHC complex serves as a highly specific neoantigen-like target for T-cell receptor (TCR) based therapies, allowing for the selective destruction of malignant cells by cytotoxic T lymphocytes. Current therapeutic development focuses on TCR-engineered T-cells (TCR-T) and TCR-like antibodies that can recognize this specific peptide-HLA configuration with high sensitivity and specificity (Source: Journal for ImmunoTherapy of Cancer, 2020).

Other names

DKK1_20-28/HLA-A*0201DKK1-P20-MHC complexALMSHGLIC-HLA-A*0201Dickkopf-1 peptide-MHC complex

Targeting of the specific peptide-MHC complex by engineered T-cell receptors (TCRs) or TCR-like antibodies to induce T-cell mediated cytotoxicity against DKK1-expressing tumor cells.