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首页> 外文期刊>Advanced Functional Materials >Bio-Hybrid Tumor Cell-Templated Capsules: A Generic Formulation Strategy for Tumor Associated Antigens in View of Immune Therapy
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Bio-Hybrid Tumor Cell-Templated Capsules: A Generic Formulation Strategy for Tumor Associated Antigens in View of Immune Therapy

机译：生物混合肿瘤细胞模板胶囊：鉴于免疫治疗肿瘤相关抗原的通用配方策略。

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摘要

For the development of effective anti-cancer vaccines, tumor associated antigens need to be internalized by antigen presenting cells alongside specific co-stimulatory signals. Interestingly, relative to soluble antigens, nano- and micro-particulate antigens are much better presented to CD8 T cells, a crucial step in the induction of cytotoxic T cells that can eliminate malignant cells. In this regard, a generic strategy to encapsulate cancer cell derived proteins into a particulate delivery system would be of high interest. Here we present a versatile approach to incorporate cancer cell proteins into polymeric capsules using the cells themselves as templates for layer-by-layer assembly of complimentary interacting species. After coating, the cells are killed by hypo-osmotic treatment leading to bio-hybrid capsules loaded with cell lysate. Particular focus is devoted in this work on choosing the optimal coating components and conditions to maximize cell membrane integrity during the coating process, minimize pre-mature protein release and achieve optimal encapsulation of cell lysate upon lysis of the cells. To further underline the generic nature of our approach, we demonstrate that heat shock proteins, important immune-activators, can be induced and encapsulated into the bio-hybrid capsules.
机译：为了开发有效的抗癌疫苗，肿瘤相关抗原需要通过抗原呈递细胞与特定的共刺激信号一起内在化。有趣的是，相对于可溶性抗原，纳米颗粒和微米颗粒抗原更好地呈递给CD8 T细胞，这是诱导可消除恶性细胞的细胞毒性T细胞的关键步骤。在这方面，将癌细胞衍生的蛋白质包封到微粒递送系统中的通用策略将是高度关注的。在这里，我们提出了一种通用的方法，可以将癌细胞蛋白质作为细胞相互作用的模板，将它们本身作为模板进行层层组装，将癌细胞蛋白质掺入聚合物胶囊中。包被后，通过低渗处理杀死细胞，从而导致载有细胞裂解物的生物混合胶囊。在这项工作中，特别着重于选择最佳的包被成分和条件，以在包被过程中最大化细胞膜的完整性，最小化过早的蛋白质释放并在细胞裂解时实现细胞裂解物的最佳包封。为了进一步强调我们方法的通用性质，我们证明了可以诱导热休克蛋白（一种重要的免疫激活剂）并将其封装到生物杂交胶囊中。

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  • 来源
    《Advanced Functional Materials》 |2014年第45期|7139-7150|共12页
  • 作者

    Lien Lybaert; Elly De Vlieghere; Riet De Rycke; Nane Vanparijs; Olivier De Wever; Stefaan De Koker; Bruno G. De Geest;

  • 作者单位

    Department of Pharmaceutics Ghent University Ottergemsesteenweg 460, 9000 Ghent, Belgium;

    Laboratory of Experimental Cancer Research Ghent University, De Pintelaan 185 9000 Ghent, Belgium;

    Department of Biomedical Molecular Biology IRC, Ghent University Technologiepark 927 9052 Zwijnaarde, Belgium, Department of Molecular Biomedical Research VIB, Ghent University Technologiepark 927 9052 Zwijnaarde, Belgium;

    Department of Pharmaceutics Ghent University Ottergemsesteenweg 460, 9000 Ghent, Belgium;

    Laboratory of Experimental Cancer Research Ghent University, De Pintelaan 185 9000 Ghent, Belgium;

    Department of Pharmaceutics Ghent University Ottergemsesteenweg 460, 9000 Ghent, Belgium, Department of Molecular Biomedical Research VIB, Ghent University Technologiepark 927 9052 Zwijnaarde, Belgium;

    Department of Pharmaceutics Ghent University Ottergemsesteenweg 460, 9000 Ghent, Belgium;

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