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How a four-domain biologic triggers T cells to kill myeloid leukemias
Amphivena Therapeutics Inc. licensed Affimed N.V.'s tetravalent antibody-mimetic technology two years ago to create blood cancer therapeutics that would be simpler to use and safer than CAR T cell therapies. Now, the start-up has presented data on AMV-564, its lead preclinical compound, and shown the compound activates T cell-mediated cytotoxicity in cell-based and mouse models of acute myelogenous leukemia (AML).
The compound targets CD3 receptors on T cells and CD33 antigens on AML cells, and is based on Affimed's TandAb (tandem diabody) platform. The platform involves fusing two heavy and two light chain variable domains from different mAbs, which forces the molecules to fold into a structure resembling four beads on a string. (See Figure: Fourbeading)...