A Novel Blockade CD47 Antibody With Therapeutic Potential for Cancer
Fangzhen Lin, Mengshang Xiong, Hao Wei, Yuewen Song, Ruoqi Liu, Yuanyuan Yang, Xiangfei Yuan, Dongmei Fan, Yizi Zhang, Yizi Zhang, Mu Hao, Ye Zhou, Lu Yang, Yanjun Zhang, Yanjun Zhang, Jianxiang Wang, Dongsheng Xiong
Abstract
Macrophages as components of the innate immune system play a critical role in antitumor responses. Strategies for targeting CD47 are becoming a hot spot for cancer therapy. The expression of CD47 is exercised by macrophages to make a distinction between “self” or “nonself.” Anti-CD47 antibodies block the interaction between macrophage signal regulatory protein-α (SIRPα) and tumor surface CD47. In this study, we report and assess a novel anti-CD47 blocking antibody named 2C8, which exhibits high affinity and tremendous anticancer effects. More concretely, 2C8 significantly induces macrophages, including protumorigenic subtype M2 macrophages killing tumor cells in vitro , and is revealed to be more effective than commercially available anti-CD47 mAb B6H12.2. In vivo, 2C8 controls tumor growth and extends survival of xenograft mice. The antitumor ability of 2C8 might be applicable to many other cancers. The generation of a novel CD47 antibody contributes to consolidating clinical interest in targeting macrophages for the treatment of malignancy and, moreover, as a supplement therapy when patients are resistant or refractory to other checkpoint therapies or relapse after such treatments.