MilatuzuMab

Milatuzumab (hLL1; MEDI-115) is a humanized anti-CD74 monoclonal antibody. CD74, a integral membrane protein, is associated with the promotion of B-cell growth and survival. Milatuzumab causes free radical oxygen generation, and loss of mitochondrial membrane potential. Milatuzumaba also decreases CD20/CD74 aggregates and cell adhesion, to lead to cell death[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

CD74[1]

Milatuzumaba（5 μg/mL；8-48 小时）增强 MCL 细胞系和原发性患者肿瘤细胞的细胞死亡[1]。 Milatuzumaba（5 μg/mL；0.5-2 h）在 Jeko、Mino 和 SP-53 细胞中介导细胞毒性，部分取决于 ROS 的产生和线粒体跨膜电位的丧失[1]。 Milatuzumaba（5 μg/mL；4 小时）抑制 NF-κB 通路并诱导细胞凋亡，凋亡机制与 caspase 裂解、Bcl-2 家族成员失调或诱导自噬无关[1]。 Western Blot Analysis[1] Cell Line: Jeko and Mino cells Concentration: 5 μg/mL Incubation Time: 4 hours Result: Insignificant down-regulation of antiapoptotic proteins, such as Bax, Bcl-2, Bcl-xL, and Mcl-1. Cell Viability Assay[1] Cell Line: MCL cell lines and primarypatient tumor cells Concentration: 5 μg/mL Incubation Time: 8, 24, and 48 hours Result: Resulted in cell death of Jeko, Mino, SP-53, Rec-1, HBL-2, and Granta cells. Immunofluorescence[1] Cell Line: Jeko, Mino, and SP-53 cells Concentration: 5 μg/mL; with or without 10 mM N-acetylcysteine (HY-B0215) for 1.5 h Incubation Time: 0.5, 1, 1.5, and 2 hours Result: Increased ROS generation as early as 0.5 hours, while peaking at 1 to 1.5 hours and reducing at 2 hours.Therefore, it resulted cell death, but reserved by nonspecific ROS scavenger.

Milatuzumaba（15 mg/kg/天；腹腔注射；每 3 天一次）显着提高携带 Jeko 癌细胞的雌性 SCID 小鼠的存活率。并且Milatuzumaba与Rituximab (HY-P9913) 在该小鼠模型中具有协同作用[1]。 Animal Model: Jeko mouse model[1] Dosage: 15 mg/kg/day; with or without 15 mg/kg Rituximab Administration: Intraperitoneal injection; once every 3 days, starting at day 15 after engraftment Result: Resulted the mean survival for the combination treated group of 44.5 days, compared with 33.5 days for Milatuzumaba treated, 28 days for control.

[1]. Alinari L, et al. Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma. Blood. 2011 Apr 28;117(17):4530-41.