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Hybrid cellular membrane nanovesicles amplify macrophage immune responses against cancer recurrence and metastasis.
- Source :
-
Nature communications [Nat Commun] 2020 Sep 30; Vol. 11 (1), pp. 4909. Date of Electronic Publication: 2020 Sep 30. - Publication Year :
- 2020
-
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.
- Subjects :
- Animals
CD47 Antigen metabolism
Cell Line, Tumor transplantation
Disease Models, Animal
Female
HEK293 Cells
Humans
Macrophage Activation drug effects
Macrophages drug effects
Macrophages metabolism
Melanoma immunology
Melanoma secondary
Membrane Proteins agonists
Membrane Proteins immunology
Mice
Nanoparticles administration & dosage
Neoplasm Recurrence, Local immunology
Nucleotides, Cyclic administration & dosage
Receptors, Immunologic metabolism
Signal Transduction drug effects
Signal Transduction immunology
Triple Negative Breast Neoplasms immunology
Tumor Escape drug effects
Tumor Escape immunology
Tumor Microenvironment immunology
Cell-Derived Microparticles immunology
Immunotherapy methods
Macrophages immunology
Melanoma therapy
Neoplasm Recurrence, Local prevention & control
Triple Negative Breast Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 32999291
- Full Text :
- https://doi.org/10.1038/s41467-020-18626-y