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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)[1][2]. | [in vivo]
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].
| Animal Model: | PBMCs-reconstituted tumor model: NSG/β2m-/- mice intradermally implanted with the KG-1a (AML-M0) cells on day 0 and intraperitoneally injected with human PBMCs on day 1[1] | | Dosage: | 0.5 μg/kg, 1 μg/kg, and 4 μg/kg; | | Administration: | Peritoneally implantation with mini-osmotic pumps; continuous infusion from days 16 to 22;
| | Result: | Inhibited tumor volume significantly. |
| [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. DOI:10.1126/scitranslmed.aaa5693
[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. DOI:10.3390/jcm11051333 |
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