title: A fully human anti-CD47 blocking antibody with therapeutic potential for cancer.
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.
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Dadi
authors.initials: D
authors.lastname: Zeng
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Chen
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Jiangfeng
authors.initials: J
authors.lastname: Fan
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Yang
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Weicai
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000074322:Antineoplastic Agents, Immunological / Q000493:pharmacokinetics / Q000494:pharmacology*; D051928:CD47 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D061505:Cell Surface Display Techniques; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D057809:HEK293 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010587:Phagocytosis / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013997:Time Factors; D020298:U937 Cells; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D000074322:Antineoplastic Agents, Immunological; D051928:CD47 Antigen; C497894:CD47 protein, human
keywords: CD47; anti-CD47 antibody; cancer therapy; cell-in-cell; phagocytosis