Activating Macrophage-Mediated Cancer Immunotherapy by Genetically Edited Nanoparticles.

Abstract

Immunomodulation of macrophages against cancer has emerged as an encouraging therapeutic strategy. However, there exist two major challenges in effectively activating macrophages for antitumor immunotherapy. First, ligation of signal regulatory protein alpha (SIRPα) on macrophages to CD47, a "don't eat me" signal on cancer cells, prevents macrophage phagocytosis of cancer cells. Second, colony stimulating factors, secreted by cancer cells, polarize tumor-associated macrophages (TAMs) to a tumorigenic M2 phenotype. Here, it is reported that genetically engineered cell-membrane-coated magnetic nanoparticles (gCM-MNs) can disable both mechanisms. The gCM shell genetically overexpressing SIRPα variants with remarkable affinity efficiently blocks the CD47-SIRPα pathway while the MN core promotes M2 TAM repolarization, synergistically triggering potent macrophage immune responses. Moreover, the gCM shell protects the MNs from immune clearance; and in turn, the MN core delivers the gCMs into tumor tissues under magnetic navigation, effectively promoting their systemic circulation and tumor accumulation. In melanoma and breast cancer models, it is shown that gCM-MNs significantly prolong overall mouse survival by controlling both local tumor growth and distant tumor metastasis. The combination of cell-membrane-coating nanotechnology and genetic editing technique offers a safe and robust strategy in activating the body's immune responses for cancer immunotherapy.

• Authors: Lang Rao, Shu-Kun Zhao, Churan Wen, Rui Tian, Lisen Lin, Bo Cai, Yue Sun, Fei Kang, Zhen Yang, Liangcan He, Jing Mu, Qian-Fang Meng, Guangyu Yao, Ni Xie, Xiaoyuan Chen
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 32 Issue 47 Pg. e2004853 (Nov 2020) ISSN: 1521-4095 [Electronic] Germany
• PMID: 33089578 (Publication Type: Journal Article)
• Copyright: © 2020 Wiley-VCH GmbH.

Topics

• Animals
• Cell Line, Tumor
• Genetic Engineering
• Humans
• Immunotherapy (methods)
• Macrophages (drug effects, immunology)
• Mice
• Nanomedicine
• Nanoparticles (chemistry)
• Neoplasms (immunology, therapy)