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    Home > Biochemistry News > Biotechnology News > Chinese scholar Nature published an article: Regulatory T cell exosomes intelligently deliver VEGF antibodies

    Chinese scholar Nature published an article: Regulatory T cell exosomes intelligently deliver VEGF antibodies

    • Last Update: 2021-07-30
    • Source: Internet
    • Author: User
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    Regulatory T cell exosomes deliver VEGF antibody for the treatment of mouse CNV: a.
    rEXS-cL-aV construction, spatio-temporal coupled delivery and anti-VEGF-anti-inflammatory synergistic treatment schematic diagram; b.
    rEXS-cL-aV transmission electron microscope Figure; c.
    rEXS-cL-aV prolongs the retention time in the eyes of mice and enhances the enrichment of CNV sites in the fundus; d.
    Basal fluorescence angiography analysis of CNV lesions in mice; e.
    Vascular endothelial cells (CD105) in choroidal tissue sections Analysis of macrophages (F4/80) and VEGF


    Based on transformable material components and clever design ideas, the creation of intelligent delivery systems is an important strategy to improve the efficacy of approved drugs
    .
    Recently, the State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, in collaboration with Beijing Chaoyang Hospital and the University of Queensland, Australia, based on exosomes derived from regulatory T cells (Treg) cleverly loaded with Vascular Endothelial Growth Factor (Vascular Endothelial Growth Factor, VEGF) antibody, through a new delivery mode and a new antagonistic mechanism, significantly inhibited the progression of fundus neovascular diseases

    .
    Related work was published on Nature Biomedical Engineering (Reduction of choroidal neovascularization via cleavable VEGF antibodies conjugated to exosomes derived from regulatory T cells, DOI:
    https://doi.
    org/10.
    1038/s41551-021-00764-3
    )
    .

    The formation of fundus neovascularization is an important link in the occurrence of various fundus diseases such as age-related macular degeneration and diabetic retinopathy.
    Without effective treatment, it will seriously affect life and work, and even cause loss of vision

    .
    The current main clinical treatment method is intravitreal injection of VEGF antibody to inhibit the growth of new blood vessels.
    However, there are still the problems of excessive metabolism of drugs with aqueous humor, difficulty in enriching fundus lesions, and limited effects of single treatment strategies

    .
    Therefore, even with multiple injections, the actual clinical response rate is only 40-60%

    .

    To this end, the State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, based on exosomes derived from Treg in vivo (rEXS) and clinically available VEGF antibody drugs, proposed "temporal and spatial coupling" delivery and "anti-VEGF-anti-inflammatory" synergistic therapy In conjunction with the new strategy of Beijing Chaoyang Hospital and the University of Queensland, the research and development of new drugs for the treatment of fundus neovascular diseases has been carried out
    .

    Based on a large number of clinical intraocular fluid samples, the research team found that fundus neovascular diseases not only contain high levels of VEGF, but also enrich a large number of inflammatory factors such as IL-6 and TNF, and there is a clear positive correlation between them.
    It reveals the close interaction between angiogenesis and inflammation in the development of fundus angiogenesis, and proposes a new idea of ​​anti-VEGF-anti-inflammatory synergistic therapy based on this

    .

    On this basis, the research team used rEXS, which has natural anti-inflammatory activity in the body, as a carrier, and connected VEGF antibody (aV) through matrix metalloproteinase (MMP) sensitive peptide (cL) to create the rEXS-cL-aV system
    .
    After intravitreal injection, the chemotaxis of rEXS to the inflammation site is used to carry aV to enrich the fundus neovascular lesions, and then the sensitive peptide cL is digested by the highly expressed MMP at the lesion site and aV is released

    .
    On the basis of the above-mentioned spatio-temporal coupled delivery, the inflammation-inhibiting effect of rEXS and the angiogenesis-inhibiting effect of aV are used to achieve synergy

    .
    Researchers have demonstrated in choroidal neovascularization (CNV) animal models in mice and cynomolgus monkeys that a single injection of rEXS-cL-aV can significantly inhibit the occurrence and development of neovascular diseases, and the effect is significantly better than the existing VEGF alone Antibody therapy strategy

    .

    According to the researchers, the above results are still animal-level preclinical studies, and the actual clinical efficacy still needs to be further verified
    .
    In view of the safety of autologous cell components and approved antibodies, the effectiveness and reproducibility of treatment results, the preparation has good clinical transformation potential

    .
    The research team is cooperating to advance the research of clinical individualized treatment in accordance with relevant requirements

    .

    In the past five years, Wei Wei, a researcher from the State Key Laboratory of Biochemical Engineering of the Institute of Process Engineering, has proposed a new strategy for biomimetic dosage form engineering.
    The natural route achieves precise delivery in vivo, and has been successfully used in targeted therapy, immunotherapy and individualized treatment in animal models, and some dosage forms have been approved by hospital ethics to enter individualized preclinical and clinical research

    .
    Related work has been published in Nat Biomed Eng 2021, 5, 414, Sci Adv 2021, 7, eabd7614, Sci Adv 2021, 7, eaba2458, Sci Adv 2020, 6, eaay7735, Sci Adv 2019, 5, eaaw3192, Nat Commun 2017, 8, 14537, Nat Commun 2019, 10, 5165, Adv Mater 2020, 32, 2002085, Adv Mater 2020, 32, 2002940, Adv Sci 2020, 7, 2001108 and other journals

    .

    Dr.
    Tian Ying and Dr.
    Zhang Fan are the co-first authors of the paper, and Prof.
    Wei Wei (Institute of Process Engineering), Prof.
    Tao Yong (Beijing Chaoyang Hospital) and Prof.
    Yu Di (University of Queensland) are the co-corresponding authors

    .
    This work was supported by the National Natural Science Foundation of China, the Science and Technology Plan Project of the Beijing Municipal Education Commission and the Talent Training Project of Beijing Chaoyang Hospital

    .


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