Flotetuzumab

Flotetuzumab (MGD006; S80880) is an investigational CD123/CD3 bispecific dual-affinity retargeting antibody (DART) molecule. Flotetuzumab reactivates T cells by simultaneously binding to CD123 in target cells and CD3 in effector T cells, leading to T-cell-mediated cytotoxicity in target cells. Flotetuzumab shows inhibitory effect on a mouse model of patient-derived xenograft (PDX) in acute myeloid leukemia (AML).

Flotetuzumab (0.01 ng/mL, 0.1 ng/mL; 144 h) increases IFN-γ, IL-10, and IL-6 secretion in primary PBMCs[1].Flotetuzumab (10-6-102 ng/mL; 24 h) shows cytotoxicity against the Kasumi-3 AML cell line using human PBMCs or cynomolgus[1].Flotetuzumab (0.01 ng/mL, 0.1 ng/mL; 6 d) dose-dependently inhibits leukemic blasts growth[1].

Flotetuzumab (0.5-4 μg/kg; intraperitoneal implantation; continuous infusion for 6 d) shows antitumor activity in human peripheral blood mononuclear cells (PBMCs)-reconstituted tumor-bearing mice[1].Flotetuzumab (0.5 mg/kg; once every 5 d; for 30 d) improves mouse survival and induces T-cell proliferation in mouse NTPL-146 patient-derived xenograft (PDX) model of acute myeloid leukemia (AML)[2].

References:
[1]. Chichili GR, et al. A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: preclinical activity and safety in nonhuman primates. Sci Transl Med. 2015 May 27;7(289):289ra82.
[2]. Barwe SP, et al. Efficacy of Flotetuzumab in Combination with Cytarabine in Patient-Derived Xenograft Models of Pediatric Acute Myeloid Leukemia. J Clin Med. 2022 Feb 28;11(5):1333.