DKK1-A2 CAR-T

DKK1-A2 CAR-T is an investigational chimeric antigen receptor T-cell therapy engineered to recognize a Dickkopf-1 (DKK1)-derived peptide presented in the context of HLA-A2 on tumor cells, enabling selective killing of DKK1-expressing, HLA-A2–positive hematologic malignancies such as multiple myeloma, lymphoma, and leukemia. DKK1 is a secreted antagonist of Wnt signaling that is overexpressed in many hematologic cancers and contributes to tumor progression and immune evasion, while being largely absent from normal adult tissues, making it an attractive tumor-associated antigen.[6][9] Preclinical studies have generated human DKK1-A2 CAR-T cells that effectively lyse cancer cells from HLA-A2+ patients with myeloma, lymphoma, or leukemia, and ongoing work is focused on optimizing Th9-polarized DKK1-A2 CAR-T products to enhance antitumor activity and potentially reduce on- and off-tumor toxicities, with the goal of advancing to first-in-human phase 1 clinical evaluation.[6]