Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis

Lang Rao, Lei Wu, Zhida Liu, Rui Tian, Guocan Yu, Zijian Zhou, Kuikun Yang, Hong-Gang Xiong, Anli Zhang, Guang-Tao Yu, Wenjing Sun, Han Xu, Jingya Guo, Andrew Li, Hongmin Chen (), Zhi-Jun Sun (), Yang-Xin Fu () and Xiaoyuan Chen ()
Additional contact information
Lang Rao: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
Lei Wu: Wuhan University
Zhida Liu: University of Texas Southwestern Medical Center
Rui Tian: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
Guocan Yu: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
Zijian Zhou: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
Kuikun Yang: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health
Hong-Gang Xiong: Wuhan University
Anli Zhang: University of Texas Southwestern Medical Center
Guang-Tao Yu: Wuhan University
Wenjing Sun: Xiamen University
Han Xu: Xiamen University
Jingya Guo: Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences
Andrew Li: Johns Hopkins University
Hongmin Chen: Xiamen University
Zhi-Jun Sun: Wuhan University
Yang-Xin Fu: University of Texas Southwestern Medical Center
Xiaoyuan Chen: National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract Effectively activating macrophages against cancer is promising but challenging. In particular, cancer cells express CD47, a ‘don’t eat me’ signal that interacts with signal regulatory protein alpha (SIRPα) on macrophages to prevent phagocytosis. Also, cancer cells secrete stimulating factors, which polarize tumor-associated macrophages from an antitumor M1 phenotype to a tumorigenic M2 phenotype. Here, we report that hybrid cell membrane nanovesicles (known as hNVs) displaying SIRPα variants with significantly increased affinity to CD47 and containing M2-to-M1 repolarization signals can disable both mechanisms. The hNVs block CD47-SIRPα signaling axis while promoting M2-to-M1 repolarization within tumor microenvironment, significantly preventing both local recurrence and distant metastasis in malignant melanoma models. Furthermore, by loading a stimulator of interferon genes (STING) agonist, hNVs lead to potent tumor inhibition in a poorly immunogenic triple negative breast cancer model. hNVs are safe, stable, drug loadable, and suitable for genetic editing. These properties, combined with the capabilities inherited from source cells, make hNVs an attractive immunotherapy.

Date: 2020
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DOI: 10.1038/s41467-020-18626-y

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