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

作者：Zeng Dadi; Sun Qiang; Chen Ang; Fan Jiangfeng; Yang Xiaopeng; Xu Lei; Du Peng; Qiu Weiyi; Zhang Weicai; Wang Shuang; Sun Zhiwei

来源：Oncotarget, 2016, 7(50): 83040-83050.

DOI：10.18632/oncotarget.13349

• CD47
• anti-CD47 antibody
• phagocytosis
• cancer therapy
• cell-in-cell

CD47/SIRPa 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.

• 出版日期2016-12-13