An in-situ peptide-antibody self-assembly to block CD47 and CD24 signaling enhances macrophage-mediated phagocytosis and anti-tumor immune responses

Weiqi Zhang, Yinghua Zeng, Qiuqun Xiao, Yuanyuan Wu, Jiale Liu, Haocheng Wang, Yuting Luo, Jie Zhan (), Ning Liao () and Yanbin Cai ()
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Weiqi Zhang: Southern Medical University
Yinghua Zeng: Southern Medical University
Qiuqun Xiao: Southern Medical University
Yuanyuan Wu: Southern Medical University
Jiale Liu: Southern Medical University
Haocheng Wang: Southern Medical University
Yuting Luo: Southern Medical University
Jie Zhan: Southern Medical University
Ning Liao: Southern Medical University
Yanbin Cai: Southern Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Targeted immunomodulation for reactivating innate cells, especially macrophages, holds great promise to complement current adaptive immunotherapy. Nevertheless, there is still a lack of high-performance therapeutics for blocking macrophage phagocytosis checkpoint inhibitors in solid tumors. Herein, a peptide-antibody combo-supramolecular in situ assembled CD47 and CD24 bi-target inhibitor (PAC-SABI) is described, which undergoes biomimetic surface propagation on cancer cell membranes through ligand-receptor binding and enzyme-triggered reactions. By simultaneously blocking CD47 and CD24 signaling, PAC-SABI enhances the phagocytic ability of macrophages in vitro and in vivo, promoting anti-tumor responses in breast and pancreatic cancer mouse models. Moreover, building on the foundation of PAC-SABI-induced macrophage repolarization and increased CD8+ T cell tumor infiltration, sequential anti-PD-1 therapy further suppresses 4T1 tumor progression, prolonging survival rate. The in vivo construction of PAC-SABI-based nano-architectonics provides an efficient platform for bridging innate and adaptive immunity to maximize therapeutic potency.

Date: 2024
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DOI: 10.1038/s41467-024-49825-6

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