T cell bi-specific antibodies are potent molecules by binding and re-directing T cells to tumor cells through tumor associate antigens (TAAs), and triggering strong T cell activation and resulting in the killing of tumor cells. Bi-specific T cell engager antibody (BITE®) has demonstrated a remarkable clinical efficacy in liquid tumor. It remains to be a tremendous challenge for the development these types of bi-specific antibodies due to the induction of cytokine storm, thus limiting the dose-escalation in patients. A new immunotherapy antibody platform, (ITab TM), was developed to generate bi-specific antibody-like molecules. The molecules target TAA and activate human CD3 T cells simultaneously. A-337 is a bi-specific antibody targeting on EpCAM (Epithelial cell adhesion molecule) on tumor cells and CD3 in human T cells. In vitro, A-337 demonstrated high potency on activating human T cell measured by CD69 expression, and killing of EpCAM highly expressing tumor cell lines with EC50 values at < 100 pM in the presence of human peripheral blood mononuclear cells (PBMC). The human PBMC dependent cell killing activity of A-337 was correlated to the expression levels of EpCAM on the surface of tumor cell lines. In the mouse model, A-337 showed dose-dependent growth inhibition of SW480 xenograft. In cynomolgus monkey studies, A-337 by single IV infusion induced peripheral T cell re-distribution or activation and cytokine release and showed favorable pharmacokinetics features. The current studies reveal that A-337 has potent anti-tumor activities in vitro and in vivo. These results demonstrate that A-337 is a promising and potent immunotherapeutic agent to treat EpCAM-expressing solid tumors and warrants further development.
Citation Format: Yumin Cui, Zhihua Huang, Hanyang Chen, Xinfeng Zhang, Bo Qi, Heng Liu, Xiaoqiang Yan. A-337, a potent bispecific antibody targeting EpCAM×CD3, as a potential immunotherapeutic agent for human solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2359.