Dickkopf-1-specific T cell receptor (DKK1-TCR)

The Dickkopf-1-specific T cell receptor (DKK1-TCR) is a specialized immune receptor that recognizes peptides derived from the Dickkopf-related protein 1 (DKK1) presented by Major Histocompatibility Complex (MHC) molecules. DKK1 is a secreted glycoprotein that acts as a potent inhibitor of the Wnt/beta-catenin signaling pathway and is highly overexpressed in various hematological and solid malignancies, such as multiple myeloma, prostate cancer, and lung cancer (UniProt O94907). In the context of immunotherapy, DKK1-specific TCRs are either naturally occurring in patients or engineered into T cells (TCR-T therapy) to direct the immune system against DKK1-expressing tumor cells (PubMed 21836165). These TCRs typically target specific immunogenic epitopes, such as DKK1-20 or DKK1-66, often in the context of HLA-A*02:01 (PubMed 33619386). By binding to these peptide-MHC complexes, the TCR triggers T cell activation, proliferation, and the release of cytotoxic granules like perforin and granzymes to induce apoptosis in cancer cells (PubMed 22431571). Therapeutic development of DKK1-TCRs aims to exploit the restricted expression pattern of DKK1 to achieve high tumor specificity and potent anti-tumor efficacy.

Other names

DKK1-specific T-cell receptorTCR specific for Dickkopf-related protein 1DKK1-targeted TCRT cell receptor on DKK1-specific CD8+ and CD4+ T cells

Recognition of DKK1-derived peptides (such as DKK1-20 or DKK1-66) presented by Major Histocompatibility Complex (MHC) molecules, typically HLA-A*02:01, on the surface of tumor cells, which triggers T cell activation, cytokine release, and direct lysis of the target cell.