A high-affinity fully human anti-IL-6 mAb (OP-R003-1, 1339) for the treatment of Multiple Myeloma

Purpose—We investigated the in vitro and in vivo anti-MM activity of mAb 1339, a high-affinity fully humanized anti-IL-6 mAb (IgG1), alone and in combination with conventional and novel anti- MM agents, as well as its effect on bone turnover. Experimental Design—We examined the growth inhibitory effect of 1339 against MM cell lines in the absence and in the presence of bone marrow stromal cells (BMSC) alone or in combination with dexamethasone, bortezomib, perifosine and revlimid. Using the SCID-hu murine model of MM, we also examined the effect of 1339 on MM cell growth and MM bone disease. Results—mAb 1339 significantly inhibited growth of MM cell in the presence of BMSC in vitro, associated with inhibition of phosphorylation of STAT3, ERK1/2 and Akt. In addition, mAb 1339 enhanced cytotoxicity induced by dexamethasone as well as bortezomib, lenalidomide, and perifosine in a synergistic fashion. Importantly mAb 1339 significantly enhanced growth inhibitory effects of dexamethasone in vivo in SCID-hu mouse model of MM. mAb 1339 treatment also resulted in inhibition of osteoclastogenesis in vitro and bone remodeling in SCID-hu model