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)[1][2].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

CD123, CD3[1]

Flotetuzumab (0.01 ng/mL, 0.1 ng/mL; 144 h) 增加原发性 PBMC 细胞 中 IFN-γ、IL-10 和 IL-6 的分泌[1]。 Flotetuzumab (10-6-102 ng/mL; 24 h) 在人或食蟹猴的 PBMC 细胞 (Kasumi-3 AML细胞系) 具有细胞毒性[1]。 Flotetuzumab (0.01 ng/mL, 0.1 ng/mL; 6 d) 剂量依赖性地抑制白血病母细胞生长[1]。 Cell Viability Assay[1] Cell Line: Primary PBMCs Concentration: 0.01 ng/mL, 0.1 ng/mL Incubation Time: 6 days Result: Resulted in a dose-dependent depletion of leukemic blasts, accompanied by a concomitant expansion of autologous T cells, up-regulation of the proliferation marker Ki-67, and a proportionally greater expansion of CD8+ cells.

Flotetuzumab (0.5-4 μg/kg; 腹腔内注入; 连续输注 6 天) 在人外周血单个核细胞 (PBMC) 重建荷瘤小鼠中显示抗肿瘤活性[1]。 Flotetuzumab (0.5 mg/kg; 每 5 天 1 次; 共 30 天) 提高小鼠 NTPL-146 患者源性异种移植 (PDX) 急性髓系白血病 (AML) 模型小鼠存活率并诱导 T 细胞增殖[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.

[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.