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首页> 外文期刊>Biological chemistry >Transcytosis of payloads that are non-covalently complexed to bispecific antibodies across the hCMEC/D3 blood-brain barrier model
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Transcytosis of payloads that are non-covalently complexed to bispecific antibodies across the hCMEC/D3 blood-brain barrier model

机译:在HCMEC / D3血脑屏障模型中非共价复合的有效载荷的转红菌症

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摘要

A transcellular shuttle system was generated for the delivery of non-covalently linked payloads across blood-brain barrier (BBB) endothelial cells. Transcytosis-enabling shuttles are composed of bispecific antibodies (bsAbs) that simultaneously bind transferrin receptor (TfR) and haptens such as digoxigenin or biocytinamide. Haptenylated payloads are attached to these vehicles via non-covalent hapten-antibody complexation. This enables targeting to and internalization into human BBB-derived microvascular endothelial hCMEC/D3 cells. In contrast to other shuttles, this system does not require special affinities or formats of their TfR-binding moieties for transcytosis and subsequent release. Non-covalent payload complexation to bsAb is flexible and robust, works for a multitude of payloads and enables separation of payloads from shuttles during transcytosis. Released payloads can enter the brain without connected bsAb entities, minimizing potential interference with distribution or functionality. Intracellular separation of shuttle and payload and recycling to cell surfaces may also enable recharging of the cell-bound BBB shuttle with payload for subsequent (merry-go-round) transport cycles.
机译:产生透晶梭系统,用于在血脑屏障(BBB)内皮细胞上递送非共价连接的有效载荷。转胞增性症 - 使能穿梭于双特异性抗体(Bsabs)组成,其同时结合转移素受体(TFR)和耐盛如靛藻素或生物霉酰胺。通过非共价Hapten-抗体络合络合将碘化的有效载荷连接到这些车辆上。这使得能够靶向和内化成为人BBB衍生的微血管内皮HCMEC / D3细胞。与其他班车相比,该系统不需要其TFR结合部分的特殊亲和力或形式用于转胞增多症和随后的释放。对BSAB的非共价有效载荷络合是灵活且鲁棒的,适用于多种有效载荷,并能够在转胞增分期间将有效载荷与梭子分离。发布的有效载荷可以在没有连接BSAB实体的情况下进入大脑,最大限度地减少与分发或功能的潜在干扰。穿梭和有效载荷的细胞内分离和回收到细胞表面也可以实现具有有效载荷的细胞结合的BBB梭子,以便随后(旋转圆形)运输循环。

著录项

  • 来源
    《Biological chemistry》 |2018年第7期|共11页
  • 作者单位

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

    Institute of Cell Biology and Immunology University of Stuttgart Allmandring 31 D-70569;

    Roche Pharma Research and Early Development (pRED) Therapeutic Modalities – Large Molecule;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    bispecific antibody; drug delivery; hapten; protein engineering; transcytosis;

    机译:双特异性抗体;药物递送;HAPTEN;蛋白质工程;转红枯病;

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