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Biomimetic cell stimulation with a graphene oxide antigen-presenting platform for developing T cell-based therapies
Nature Nanotechnology ( IF 38.1 ) Pub Date : 2024-09-23 , DOI: 10.1038/s41565-024-01781-4
Enbo Zhu, Jiaji Yu, Yan-Ruide Li, Feiyang Ma, Yu-Chen Wang, Yang Liu, Miao Li, Yu Jeong Kim, Yichen Zhu, Zoe Hahn, Yang Zhou, James Brown, Yuchong Zhang, Matteo Pelegrini, Tzung Hsiai, Lili Yang, Yu Huang

Chimeric antigen receptor (CAR)-engineered T cells represent a front-line therapy for cancers. However, the current CAR T cell manufacturing protocols do not adequately reproduce immunological synapse formation. Here, in response to this limitation, we have developed a flexible graphene oxide antigen-presenting platform (GO-APP) that anchors antibodies onto graphene oxide. By decorating anti-CD3 (αCD3) and anti-CD28 (αCD28) on graphene oxide (GO-APP3/28), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP3/28 and T cells closely mimic the in vivo immunological synapses between antigen-presenting cells and T cells. This immunological synapse mimicry shows a high capacity for stimulating T cell proliferation while preserving their multifunctionality and high potency. Meanwhile, it enhances CAR gene-engineering efficiency, yielding a more than fivefold increase in CAR T cell production compared with the standard protocol. Notably, GO-APP3/28 stimulated appropriate autocrine interleukin-2 (IL-2) in T cells and overcame the in vitro reliance on external IL-2 supplementation, offering an opportunity to culture T cell-based products independent of IL-2 supplementation.



中文翻译:


使用氧化石墨烯抗原呈递平台进行仿生细胞刺激,用于开发基于 T 细胞的疗法



嵌合抗原受体 (CAR) 工程 T 细胞代表了癌症的一线疗法。然而,目前的 CAR T 细胞制造方案并不能充分重现免疫突触的形成。在这里,为了应对这一限制,我们开发了一种灵活的氧化石墨烯抗原呈递平台(GO-APP),将抗体锚定在氧化石墨烯上。通过在氧化石墨烯 (GO-APP 3/28 ) 上修饰抗 CD3 (αCD3) 和抗 CD28 (αCD28),我们实现了显着的 T 细胞增殖。 GO-APP 3/28和 T 细胞之间的体外相互作用密切模仿抗原呈递细胞和 T 细胞之间的体内免疫突触。这种免疫突触拟态显示出刺激 T 细胞增殖的高能力,同时保留其多功能性和高效力。同时,它提高了CAR基因工程效率,与标准方案相比,CAR T细胞产量增加了五倍以上。值得注意的是,GO-APP 3/28刺激了 T 细胞中适当的自分泌白细胞介素 2 (IL-2),并克服了体外对外部 IL-2 补充剂的依赖,为培养独立于 IL-2 的基于 T 细胞的产品提供了机会补充。

更新日期:2024-09-25
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