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Abstract
Choroidal neovascularization induced by age-related macular degeneration and retinal neovascularization induced by diabetic retinopathy—two leading causes of blindness—are often treated using antibodies targeting vascular endothelial growth factor (VEGF). Here we report a strong association between inflammation and high VEGF expression in aqueous humour samples from patients with choroidal or retinal neovascularization, and show that intravitreally injected exosomes derived from regulatory T cells and conjugated with an anti-VEGF antibody via a peptide linker that is cleavable by matrix metalloproteinases markedly suppressed ocular neovascularization in mouse and non-human primate models of choroidal neovascularization. The engineered exosomes, which selectively accumulate in the neovascularization lesions, could be adapted for other combination therapies of therapeutic antibodies and anti-inflammatory cargo.
Intravitreally injected exosomes derived from regulatory T cells and conjugated with an antibody for vascular endothelial growth factor via a cleavable linker markedly suppress ocular neovascularization in mice and non-human primates.
Details
; Yu, Di 8
; Wei, Wei 5
1 Beijing Chaoyang Hospital, Capital Medical University, Department of Ophthalmology, Beijing, P. R. China (GRID:grid.411607.5); Institute of Process Engineering, Chinese Academy of Sciences, State Key Laboratory of Biochemical Engineering, Beijing, P. R. China (GRID:grid.458442.b) (ISNI:0000 0000 9194 4824)
2 Institute of Process Engineering, Chinese Academy of Sciences, State Key Laboratory of Biochemical Engineering, Beijing, P. R. China (GRID:grid.458442.b) (ISNI:0000 0000 9194 4824); Sun Yat-Sen University, School of Pharmaceutical Sciences (Shenzhen), Shenzhen, P. R. China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X)
3 Animal Center of the Academy of Military Medical Sciences, Beijing, P. R. China (GRID:grid.410740.6) (ISNI:0000 0004 1803 4911)
4 Institute of Process Engineering, Chinese Academy of Sciences, State Key Laboratory of Biochemical Engineering, Beijing, P. R. China (GRID:grid.458442.b) (ISNI:0000 0000 9194 4824)
5 Institute of Process Engineering, Chinese Academy of Sciences, State Key Laboratory of Biochemical Engineering, Beijing, P. R. China (GRID:grid.458442.b) (ISNI:0000 0000 9194 4824); University of Chinese Academy of Sciences, School of Chemical Engineering, Beijing, P. R. China (GRID:grid.410726.6) (ISNI:0000 0004 1797 8419)
6 Beijing Institute of Biotechnology, State Key Laboratory of Pathogen and Biosecurity, Beijing, P. R. China (GRID:grid.43555.32) (ISNI:0000 0000 8841 6246)
7 Beijing Chaoyang Hospital, Capital Medical University, Department of Ophthalmology, Beijing, P. R. China (GRID:grid.411607.5)
8 The University of Queensland, The University of Queensland Diamantina Institute, Faculty of Medicine, Brisbane, Australia (GRID:grid.1003.2) (ISNI:0000 0000 9320 7537)