Sar650984, An Anti-Cd38 Antibody, Shows Anti-Tumor Activity In A Preclinical Model Of Multiple Myeloma.

Multiple myeloma (MM) is the second most common cancer of the blood and one that is difficult to treat. Although survival has greatly improved over the past decade, MM remains fatal, necessitating development of novel therapies. CD38 is a promising target for antibody therapeutics for the treatment MM and various other hematological malignancies. CD38 is a type II transmembrane glycoprotein with ectozyme activity that has been implicated in Ca2+ mobilization and is found highly expressed on malignant plasma cells of MM. CD38 expression correlates with poor disease prognosis in a subset of hematological malignancies, including MM, where CD38 expression in circulating cells is associated with decreased progression free survival. Previous studies have identified several potential mechanisms of action in the context of anti-myeloma activity, including antibody-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and pro-apoptotic activity in cancer cell lines. To determine the potential therapeutic value of targeting CD38 in the context of MM, a humanized anti-CD38 antibody, SAR650984, was generated and evaluated for anti-tumor activity. We evaluated anti-tumor activity of SAR650984 in xenograft-based models of multiple myeloma . SAR650984 demonstrated potent anti-tumor activity in NCI-H929 and RPMI-8226 MM xenograft models. These results strongly support continued clinical examination of the therapeutic potential for SAR650984 in the treatment of MM and further demonstrates that targeting CD38 with SAR650984 has potential to impact MM disease. Citation Format: Byron Hann, Ti Cai, Donghui Wang, Yun-Kit Hom, Blake T. Aftab, Tom Martin, Jeffrey Wolf. SAR650984, an anti-CD38 antibody, shows anti-tumor activity in a preclinical model of multiple myeloma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5469. doi:10.1158/1538-7445.AM2013-5469