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Published on: November 12, 2019
A fully human anti-CD47 blocking antibody with therapeutic potential for cancer
Dadi Zeng1, Qiang Sun1, Ang Chen1
1Beijing Institute of Biotechnology, Fengtai District, Beijing 100071, China.
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.
Insights
Researchers isolated ZF1, a fully human antibody targeting CD47, to block immune checkpoints. This antibody effectively promotes cancer cell phagocytosis and offers preclinical promise for leukemia treatment.
Area of Science:
- Immunology
- Oncology
- Biotechnology
Background:
- CD47/SIRPα interaction is a key immune checkpoint regulating macrophage phagocytosis.
- Mouse anti-CD47 antibodies show preclinical efficacy in cancer but a fully human antibody is needed for clinical applications.
Purpose of the Study:
- To isolate and characterize a fully human anti-CD47 blocking antibody for potential leukemia therapy.
- To evaluate the efficacy of the novel antibody ZF1 in preclinical cancer models.
Main Methods:
- Isolation of a fully human anti-CD47 antibody (ZF1) using phage display technology.
- Assessment of ZF1's specificity and affinity for CD47.
- In vitro evaluation of ZF1-induced phagocytosis of leukemic cells by macrophages.
- In vivo efficacy studies in mouse models bearing human leukemic cells.
Main Results:
- ZF1 demonstrated high specificity and affinity for CD47, comparable to existing humanized antibodies.
- ZF1 significantly enhanced macrophage-mediated phagocytosis of leukemic cells in vitro.
- ZF1 provided protection against leukemia in vivo, similar to the humanized antibody B6H12.
Conclusions:
- ZF1 is a potent, fully human anti-CD47 blocking antibody with promising preclinical efficacy.
- ZF1 represents a potential therapeutic candidate for treating human leukemia by targeting the CD47 immune checkpoint.
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