2. Academic Validation
  3. Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells

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.
Ying Tian  # 1 2,  Fan Zhang  # 2 3,  Yefeng Qiu 4,  Shuang Wang 2,  Feng Li 2 5,  Jiawei Zhao 2,  Chao Pan 6,  Yong Tao 7,  Di Yu 8,  Wei Wei 9 10
Affiliations

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.

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