School of Life Science, Beijing Institute of Technology , Beijing 100081, P. R. China.
National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, P. R. China.
ACS Nano. 2017 Nov 28;11(11):10724-10732. doi: 10.1021/acsnano.7b04955. Epub 2017 Sep 20.
Adoptive T-cell transfer for cancer therapy relies on both effective ex vivo T-cell expansion and in vivo targeting performance. One promising but challenging method for accomplishing this purpose is to construct multifunctional artificial antigen-presenting cells (aAPCs). We herein developed biomimetic magnetosomes as versatile aAPCs, wherein magnetic nanoclusters were coated with azide-engineered leucocyte membranes and then decorated with T-cell stimuli through copper-free click chemistry. These nano aAPCs not only exhibited high performance for antigen-specific cytotoxic T-cell (CTL) expansion and stimulation but also visually and effectively guided reinfused CTLs to tumor tissues through magnetic resonance imaging and magnetic control. The persisting T cells were able to delay tumor growth in a murine lymphoma model, while the systemic toxicity was not notable. These results together demonstrated the excellent potential of this "one-but-all" aAPC platform for T-cell-based anticancer immunotherapy.
过继性 T 细胞转移疗法依赖于有效的体外 T 细胞扩增和体内靶向性能。一种有前途但具有挑战性的方法是构建多功能人工抗原呈递细胞 (aAPC)。本研究开发了仿生磁小体作为多功能 aAPC,其中磁性纳米簇用叠氮化物工程化的白细胞膜包裹,然后通过无铜点击化学用 T 细胞刺激物进行修饰。这些纳米 aAPC 不仅表现出高效的抗原特异性细胞毒性 T 细胞 (CTL) 扩增和刺激作用,而且通过磁共振成像和磁控制,能够可视化并有效地引导重输注的 CTL 转移到肿瘤组织。持续存在的 T 细胞能够延迟小鼠淋巴瘤模型中的肿瘤生长,而全身毒性并不明显。这些结果共同证明了这种“一触即发”的 aAPC 平台在基于 T 细胞的抗癌免疫治疗中的巨大潜力。
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