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// Dadi Zeng 1, * , Qiang Sun 1, * , Ang Chen 1 , Jiangfeng Fan 1 , Xiaopeng Yang 1 , Lei Xu 1 , Peng Du 1 , Weiyi Qiu 1 , Weicai Zhang 1 , Shuang Wang 1 , Zhiwei Sun 1 1 Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China * These two authors contributed equally to this work Correspondence to: Zhiwei Sun, email: szwyhhh@aliyun.com Shuang Wang, email: 18910810680@163.com Weicai Zhang, email: drzhangweicai@163.com Keywords: CD47, anti-CD47 antibody, phagocytosis, cancer therapy, cell-in-cell Received: March 17, 2016 Accepted: October 17, 2016 Published: November 15, 2016 ABSTRACT CD47/SIRPα interaction serves as an immune checkpoint for macrophage-mediated phagocytosis. Mouse anti-CD47 blocking antibodies had demonstrated potent efficacy in the treatment of both leukemic and solid tumors in preclinical experimentations, and therefore had moved forward rapidly into clinical trials. However, a fully human blocking antibody, which meets clinical purpose better, has not been reported for CD47 up to date. In this study, we reported the isolation of a fully human anti-CD47 blocking antibody, ZF1, from a phage display library. ZF1 displayed high specificity and affinity for CD47 protein, which were comparable to those for humanized anti-CD47 blocking antibody B6H12. Importantly, ZF1 treatment could induce robust, or even stronger than B6H12, phagocytosis of leukemic cancer cells by macrophage in vitro , and protect BALB/c nude mice from cancer killing by engrafted leukemic cells (CCRF and U937) to a similar extent as B6H12 did. Thus, these data provide primary early pre-clinical support for the development of ZF1 as a fully human blocking antibody to treat human leukemia by targeting CD47 molecule.