Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells
- Nat Biomed Eng. 2021 Sep;5(9):968-982. doi: 10.1038/s41551-021-00764-3.
- 1. Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China.
- 2. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China.
- 3. School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, P. R. China.
- 4. Animal Center of the Academy of Military Medical Sciences, Beijing, P. R. China.
- 5. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China.
- 6. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Beijing, P. R. China.
- 7. Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P. R. China. [email protected].
- 8. The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. [email protected].
- 9. State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P. R. China. [email protected].
- 10. School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P. R. China. [email protected].
- # Contributed equally.
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.