Oncotarget

Research Papers:

A fully human anti-CD47 blocking antibody with therapeutic potential for cancer

Dadi Zeng, Qiang Sun, Ang Chen, Jiangfeng Fan, Xiaopeng Yang, Lei Xu, Peng Du, Weiyi Qiu, Weicai Zhang, Shuang Wang and Zhiwei Sun _

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Oncotarget. 2016; 7:83040-83050. https://doi.org/10.18632/oncotarget.13349

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Abstract

Dadi Zeng1,*, Qiang Sun1,*, Ang Chen1, Jiangfeng Fan1, Xiaopeng Yang1, Lei Xu1, Peng Du1, Weiyi Qiu1, Weicai Zhang1, Shuang Wang1, Zhiwei Sun1

1Beijing 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.


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