Zhu Enbo, Yu Jiaji, Li Yan-Ruide, Ma Feiyang, Wang Yu-Chen, Liu Yang, Li Miao, Kim Yu Jeong, Zhu Yichen, Hahn Zoe, Zhou Yang, Brown James, Zhang Yuchong, Pelegrini Matteo, Hsiai Tzung, Yang Lili, Huang Yu
Department of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Nat Nanotechnol. 2024 Dec;19(12):1914-1922. doi: 10.1038/s41565-024-01781-4. Epub 2024 Sep 23.
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-APP), we achieved remarkable T cell proliferation. In vitro interactions between GO-APP 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-APP 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.
嵌合抗原受体(CAR)工程化T细胞是癌症的一线治疗方法。然而,目前的CAR T细胞制造方案不能充分重现免疫突触的形成。在此,针对这一局限性,我们开发了一种灵活的氧化石墨烯抗原呈递平台(GO-APP),该平台将抗体锚定在氧化石墨烯上。通过在氧化石墨烯(GO-APP)上修饰抗CD3(αCD3)和抗CD28(αCD28),我们实现了显著的T细胞增殖。GO-APP与T细胞之间的体外相互作用紧密模拟了抗原呈递细胞与T细胞之间的体内免疫突触。这种免疫突触模拟显示出在保留T细胞多功能性和高效力的同时,具有刺激T细胞增殖的高能力。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多。值得注意的是,GO-APP刺激T细胞产生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补充的依赖,为独立于IL-2补充培养基于T细胞的产品提供了机会。