Bp-Bs, a Novel T-cell Engaging Bispecific Antibody with Biparatopic Her2 Binding, Has Potent Anti-tumor Activities

作者：Jiayu Liu, Xiaoqiong Wu, Limin Lin, Haitao Pan, Yanlan Wang, Yumei Li, Yining Zhao, Zhong Wang · 发表于：Molecular Therapy — Oncolytics · 年份：2019 · DOI：10.1016/j.omto.2019.03.009 · 被引用次数：16 · 研究领域：Monoclonal and Polyclonal Antibodies Research、HER2/EGFR in Cancer Research、CAR-T cell therapy research

Patients with Human epidermal growth factor receptor type 2 (Her2) overexpression are associated with aggressive tumor growth and poor clinical outcomes. Bispecific antibodies targeting Her2 have recently exhibited potent effects on Her2 signal inhibition. In this study, a novel biparatopic anti-Her2 bispecific antibody (Bp-Bs) was constructed by linking a single anti-CD3 Fab with two different anti-Her2 single-domain antibodies targeting non-overlapping epitopes of Her2. The Bp-Bs demonstrated strong binding on Her2-positive cells and potent cytotoxicity on Her2-positive tumor cells, even Her2-low expression cells, suggesting that biparatopic bispecific antibodies may have improved therapeutic benefits on broad Her2 patient populations.