Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells

Ying Tian; Fan Zhang; Yefeng Qiu; Shuang Wang; Feng Li; Jiawei Zhao; Chao Pan; Yong Tao; Di Yu; Wei Wei

doi:10.1038/s41551-021-00764-3

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. Epub 2021 Jul 26.

Authors

Ying Tian^#^{1

2}, Fan Zhang^#^{2

3}, Yefeng Qiu⁴, Shuang Wang², Feng Li^{2

5}, Jiawei Zhao², Chao Pan⁶, Yong Tao⁷, Di Yu⁸, Wei Wei^{9

10}

Affiliations

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.

PMID: 34312509
DOI: 10.1038/s41551-021-00764-3

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Choroidal Neovascularization* / therapy
Exosomes*
Humans
Mice
T-Lymphocytes, Regulatory
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors

Substances

Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors