TY - JOUR
T1 - Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis
AU - Rao, Lang
AU - Wu, Lei
AU - Liu, Zhida
AU - Tian, Rui
AU - Yu, Guocan
AU - Zhou, Zijian
AU - Yang, Kuikun
AU - Xiong, Hong Gang
AU - Zhang, Anli
AU - Yu, Guang Tao
AU - Sun, Wenjing
AU - Xu, Han
AU - Guo, Jingya
AU - Li, Andrew
AU - Chen, Hongmin
AU - Sun, Zhi Jun
AU - Fu, Yang Xin
AU - Chen, Xiaoyuan
N1 - Publisher Copyright:
© 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85091718864&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091718864&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-18626-y
DO - 10.1038/s41467-020-18626-y
M3 - Article
C2 - 32999291
AN - SCOPUS:85091718864
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 4909
ER -