Open AccessPreclinical efficacy and toxicity studies of a highly specific chimeric anti‐CD47 antibody
Author(s) -
Xu Zhiqiang,
Gao Jing,
Yao Jingyun,
Yang Teddy,
Wang Dongxu,
Dai Chaohui,
Ding Yu
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13084
Subject(s) - cd47 , antibody , toxicity , in vivo , immunotherapy , immune system , in vitro , phagocytosis , cancer immunotherapy , cancer research , antigen , immunology , biology , chemistry , biochemistry , microbiology and biotechnology , organic chemistry
Cluster of differentiation 47 (CD47) is a widely expressed self‐protection transmembrane protein that functions as a critical negative regulator to induce macrophage‐mediated phagocytosis. Overexpression of CD47 enables cancer cells to escape immune surveillance and destruction by phagocytes both in solid tumours and leukaemia. The usefulness of anti‐CD47 antibody has been demonstrated in multiple immunotherapies associated with macrophages. However, antigen sinks and toxicity induced by inadvertent binding to normal cells restrict its clinical applications. Here, a novel anti‐human CD47 antibody, 4D10, was generated, and its variable regions were grafted onto a human IgG4 scaffold. Compared with the anti‐CD47 antibody Hu5F9, the resulting chimeric antibody (c4D10) has consistently demonstrated good tolerance in in vitro and in vivo toxicity studies. Additionally, c4D10 showed effective therapeutic potential through inducing the eradication of human cancer cells. Thus, c4D10 is a promising candidate therapeutic antibody with higher efficacy and reduced side effects compared to earlier antibodies, and its use may reduce the dose‐limiting toxicity of CD47 antagonists for immunotherapy.