Ferritin is a multivalent, self-assembling protein scaffold found in most human cell types, in addition to being present in invertebrates, higher plants, fungi, and bacteria, that offers an attractive alternative to polymer-based drug delivery systems (DDS). In this study, the utility of the ferritin cage as a DDS was demonstrated within the context of T cell agonism for tumor killing. Members of the tumor necrosis factor receptor superfamily (TNFRSF) are attractive targets for the development of anticancer therapeutics. These receptors are endogenously activated by trimeric ligands that occur in transmembrane or soluble forms, and oligomerization and cell-surface anchoring have been shown to be essential aspects of the targeted agonism of this receptor class. Here, we demonstrated that the ferritin cage could be easily tailored for multivalent display of anti-OX40 antibody fragments on its surface and determined that these arrays are capable of pathway activation through cell-surface clustering. Together, these results confirm the utility, versatility, and developability of ferritin as a DDS.

中文翻译：

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采用铁蛋白（一种天然存在的蛋白笼）来调节 OX40 的内在激动作用

铁蛋白是一种多价自组装蛋白质支架，存在于大多数人类细胞类型中，此外还存在于无脊椎动物、高等植物、真菌和细菌中，为基于聚合物的药物递送系统 (DDS) 提供了一种有吸引力的替代方案。在这项研究中，铁蛋白笼作为 DDS 的效用在 T 细胞激动杀伤肿瘤的背景下得到了证明。肿瘤坏死因子受体超家族（TNFRSF）的成员是抗癌疗法开发的有吸引力的目标。这些受体被跨膜或可溶形式的三聚配体内源性激活，寡聚化和细胞表面锚定已被证明是此类受体靶向激动的重要方面。在这里，我们证明了铁蛋白笼可以很容易地定制，以便在其表面上多价展示抗 OX40 抗体片段，并确定这些阵列能够通过细胞表面聚类激活通路。总之，这些结果证实了铁蛋白作为 DDS 的实用性、多功能性和可开发性。