Definition

A multi-specific T-cell engaging designed ankyrin repeat proteins (DARPin) composed of a chain of six covalently linked DARPin domains of which three domains target the three tumor-associated antigens (TAAs) cluster of differentiation 33 (CD33), CD123 and CD70, one domain targets CD3 on T cells and two domains target human serum albumin (HSA) to prolong half-life, with potential immunomodulating and antineoplastic activities. Upon administration, anti-CD33/CD123/CD70 DARPin CD3 engager MP0533 selectively targets and binds to CD33, CD123 and CD70 that are expressed on a variety of tumor cells. The simultaneous binding of the CD3-targeting DARPin domain of MP0533 to T cells results in local clustering of the TAA-expressing tumor cells and T cells, and local immune cell activation through the promotion of T-cell activation, cytokine and chemokine release and T-cell-mediated anti-tumor immune responses. CD33, CD123 and CD70 are all present on acute myeloid leukemia (AML) cells and are more likely to be expressed together on AML blast cells and leukemic stem cells (LSCs) than on healthy cells, such as hematopoietic stem cells (HSCs), that may express a single TAA. The binding of MP0533 to either two or three TAAs enhances its selectivity for AML cells over healthy cells.