Researchers at the Institute of Process Engineering (IPE) of the Chinese Academy of Sciences, Beijing Chaoyang Hospital and the University of Queensland have developed a new formulation based on regulatory T-cell exosomes (rEXS) to generate antibodies against vascular endothelial growth factor (VEGF ) for choroidal neovascularization therapy.
The study was published in Nature Biomedical Engineering on July 26th.
Ocular neovascularization is often associated with age-related macular degeneration, diabetic retinopathy, and other eye conditions that can lead to severe vision loss.
The current treatment for neovascular eye disease in the clinic is intravitreal injection of VEGF antibodies (aV) to block the activity of VEGF and suppress pathogenic angiogenesis. However, this therapy alone has problems with rapid metabolism with the aqueous humor, low accumulation in lesions, and limited effectiveness. A significant proportion of patients still show an incomplete response to treatment with the above aV.
In this study, researchers collected aqueous humor samples from a large cohort of patients and quantified VEGF and other proinflammatory cytokines. “We observed a strong association between inflammation and high VEGF expression in aqueous humor samples,” said Prof. TAO Yong from Beijing Chaoyang Hospital. Therefore, they proposed a synergistic therapeutic approach that combines anti-VEGF and anti-inflammatory therapies.
Following this approach, exosomes isolated from regulatory T cells were used to conjugate aV using a peptide linker (cL) that was cleaved in inflammatory lesions by matrix metalloproteinases (MMPs). “With this design concept, an efficient spatiotemporal delivery for the combination therapy could be achieved. After intravitreal injection, rEXS-cL-aV used the ability of rEXS to locate itself in neovascularization lesions and, after MMP-mediated cleavage, released rEXS and aV to suppress inflammation and VEGF activity, ”said Prof. WEI Wei from the IPE .
The potent therapeutic efficacy has been confirmed in both murine and non-human primate models of choroidal neovascularization. “This study is still in the preclinical stage. Since rEXS can be made from the patient’s own cells and aV is approved for clinical use, our rEXS-cL-aV has the potential to be transferred to the clinic, ”said Prof. YU Di from the University of Queensland.
A peer reviewer of Nature Biomedical Engineering said, “The technology is new and the treatment efficacy is impressive.” The reviewer also emphasized that “the work as a whole represents a significant technological and potentially therapeutic advance for the treatment of neovascular diseases”.