Manchester Collaborative Center for Inflammation Research , University of Manchester , 46 Grafton Street , Manchester M13 9NT , United Kingdom.
Nano Lett. 2018 May 9;18(5):3282-3289. doi: 10.1021/acs.nanolett.8b01089. Epub 2018 Apr 20.
An emerging new paradigm is that immune cell activation is controlled by transient interactions between supramolecular assemblies of receptors and ligands. Current immunotherapy biologic pharmaceuticals that activate or desensitize NK cells are, however, individual molecules that do not replicate this nanoscale organization of proteins. Here, we use nanoscale graphene oxide (NGO) as a template to generate soluble nanoscale clusters of Natural Killer cell-activating antibodies. We control nanocluster size and molecular number to mimic reported values for cell surface proteins. These NGO-templated molecular nanoclusters, used to stimulate NK cells via the CD16 receptor, successfully induced cellular activation, indicated by degranulation of cytolytic granules and IFN-γ secretion. Importantly, activation significantly exceeded that induced by the same antibodies applied as a solution of individual molecules. These results demonstrate that future immunotherapies could be enhanced by assembling immunomodulatory drugs into nanoclusters and establish NGO-templating as a candidate technology.
一个新兴的新范式是，免疫细胞的激活是由受体和配体的超分子组装体之间的瞬时相互作用控制的。然而，目前激活或脱敏 NK 细胞的免疫治疗生物制药是单个分子，无法复制这种蛋白质的纳米级组织。在这里，我们使用纳米级氧化石墨烯（NGO）作为模板来生成天然杀伤细胞激活抗体的可溶性纳米级簇。我们控制纳米簇的大小和分子数量，以模拟报道的细胞表面蛋白的值。这些通过 CD16 受体刺激 NK 细胞的 NGO 模板化分子纳米簇成功地诱导了细胞活化，表现为细胞毒性颗粒的脱粒和 IFN-γ 的分泌。重要的是，这种激活作用大大超过了相同抗体作为单个分子溶液所引起的激活作用。这些结果表明，通过将免疫调节药物组装成纳米簇，可以增强未来的免疫疗法，并确立 NGO 模板作为候选技术。
