Milatuzumab (MEDI-115) is a humanized monoclonal antibody against CD74. Milatuzumab promotes the production of free radical oxygen and the loss of mitochondrial membrane potential, reduces CD20/CD74 aggregates and cell adhesion, and induces cell death.

Milatuzumab (5 μg/mL; 8-48 hours) enhanced cell death in MCL cell lines and primary patient tumor cells[1].
In Jeko, Mino, and SP-53 cells, milatuzumab (5 μg/mL; 0.5-2 h) mediated cytotoxicity, depending in part on ROS production and loss of mitochondrial transmembrane potential[1].
Milatuzumab (5 μg/mL; 4 hours) inhibited the NF-κB pathway and induced apoptosis. The mechanism of apoptosis was not related to caspase cleavage, Bcl-2 family member disorder, or autophagy induction[1].

Administered at a dose of 15 mg/kg/day via intraperitoneal injection every 3 days, milatuzumab significantly increased the survival rate of female SCID mice carrying Jeko cancer cells. Additionally, Milatuzumab and Rituximab demonstrated a synergistic effect in this mouse model[1].