Ulocuplumab (Anti-Human CXCR4 Recombinant Antibody/BMS-936564/MDX1338) is a fully human IgG4 anti-CXCR4 antibody. Ulocuplumab induces apoptosis and inhibits CXCL12 mediated CXCR4 activation-migration of chronic lymphocytic leukemia (CLL). Ulocuplumab exhibits antitumor activity in established tumors including acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL), and multiple myeloma xenograft models.
Ulocuplumab (0-100 μM; 48 h) lacks antibody dependent cellular cytotoxicity (ADCC) or complement (CDC) activity, but also induces apoptosis mediated by CXCR4 binding in Ramos cells and CLL/cancer cell lines, also shows pro-apoptotic in primary leukemia cells from CLL patients[1].Ulocuplumab (0.2 μM and 2 μM; 15 s) inhibits F-actin polymerization and reduces the peak response to CXCL12, and also (20 nM-2 μM; 1 h) inhibits cell migration[1].Ulocuplumab (200 nM; 6 h) leads to induction of programmed cell death (PCD) is caspase independent[1].Ulocuplumab (10 μg/mL; 4 h) induces cell death via production of reactive oxygen species (ROS) in CLL cells[1].Ulocuplumab inhibits CXCL12-induced calcium flux with an EC50 value of 10 nM in Ramos[2].
Ulocuplumab (3-30 mg/kg; i.p.; every 3-4 days for 5 doses; 65 days in total) inhibits tumor growth of multiple myeloma xenograft models in mice, including Ramos B cells, HL-60 cells, MOLP-8 cells, Nomo-1 cells, and JJN-3R cells models[1].
References:
[1]. Kasap MK, et al. Ulocuplumab (BMS-936564 / MDX1338): a fully human anti-CXCR4 antibody induces cell death in chronic lymphocytic leukemia mediated through a reactive oxygen species-dependent pathway. Oncotarget. 2016 Jan 19;7(3):2809-22.
[2]. Kuhne MR, et al. BMS-936564/MDX-1338: a fully human anti-CXCR4 antibody induces apoptosis in vitro and shows antitumor activity in vivo in hematologic malignancies. Clin Cancer Res. 2013 Jan 15;19(2):357-66.