33C2-SDIE

33C2-SDIE is an Fc-optimized monoclonal antibody targeting C-type lectin domain family 12 member A (CLEC12A), also known as CLL-1. It is designed for the treatment of acute myeloid leukemia (AML), where CLEC12A is abundantly expressed on leukemic cells and stem cells but absent on healthy hematopoietic stem cells. The antibody features an 'SDIE' Fc-optimization (typically S239D/I332E mutations) to enhance its affinity for Fcγ receptors, thereby increasing antibody-dependent cellular cytotoxicity (ADCC). In the context of the MIC12 program, 33C2-SDIE serves as the targeting moiety for a modified immunocytokine, where it is fused to an IL-15E46K mutant. This mutant lacks binding to IL-15Rα, ensuring that IL-15 activity is restricted to the tumor site upon antigen binding by the 33C2-SDIE component, thereby reducing systemic toxicity while promoting NK and T cell activation.