Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, Department of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, 518060, China.
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.
Small. 2021 Apr;17(14):e2006955. doi: 10.1002/smll.202006955. Epub 2021 Mar 12.
T cell based-immunotherapy has been a powerful strategy to eradicate tumor cells in clinical trials. Effectively expanding the therapeutic T cells for clinical demand is still a challenge. Here, artificial antigen-presenting scaffolds are created for T cell ex vivo expansion. The antigen-presenting hybrid colloidal crystal clusters (HCCCs) with multiple stimuli are generated by internal encapsulation with prosurvival cytokines and surface decoration with activating antibodies to CD3ε and CD28, respectively. With the large loading capacity endowed by their abundant nanoporous structures, the antigen-presenting HCCCs can constantly release prosurvival cytokine IL-2. It is found that following the direct and multiple stimulations, the antigen-presenting HCCCs can effectively promote the expansion of T cells, which exhibits robust antitumor activity in vitro. Thus, the antigen-presenting HCCCs provide a novel expansion platform for clinical manufacturing of T cells.
基于 T 细胞的免疫疗法已成为临床试验中消除肿瘤细胞的一种强大策略。然而,有效地扩增治疗性 T 细胞以满足临床需求仍然是一个挑战。在这里,我们构建了一种人工抗原呈递支架,用于 T 细胞的体外扩增。通过内部包封具有生存能力的细胞因子和表面修饰分别带有激活抗体 CD3ε 和 CD28,制备了具有多种刺激的抗原呈递混合胶体晶体簇(HCCCs)。由于其丰富的纳米多孔结构赋予的大容量负载能力,抗原呈递 HCCCs 可以持续释放生存能力的细胞因子 IL-2。研究发现,经过直接和多次刺激后,抗原呈递 HCCCs 可以有效地促进 T 细胞的扩增,在体外表现出强大的抗肿瘤活性。因此,抗原呈递 HCCCs 为 T 细胞的临床制造提供了一种新的扩增平台。