Department of Pharmaceutical Sciences, University of Michigan, Biointerfaces Institute, University of Michigan, 2800 Plymouth Drive, Ann Arbor, MI, 48109, USA.
Department of Biomedical Engineering, University of Michigan, 2800 Plymouth Drive, Ann Arbor, MI, 48109, USA.
Adv Healthc Mater. 2019 Feb;8(4):e1801091. doi: 10.1002/adhm.201801091. Epub 2018 Nov 22.
Cell membranes have recently gained attention as a promising drug delivery system. Here, dendritic cell membrane vesicles (DC-MVs) are examined as a platform to promote T cell responses. Nanosized DC-MVs are derived from DCs pretreated with monophosphoryl lipid A (MPLA), a FDA-approved immunostimulatory adjuvant. These "mature" DC-MVs activate DCs in vitro and increase their expression of costimulatory markers. DC-MVs also promote cross-priming of antigen-specific T cells in vitro, increasing their survival and CD25 expression. In addition, these mature DC-MVs potently augment the expansion of adoptively transferred CD8+ T cells in vivo, generating twofold to fourfold higher frequency of antigen-specific T cells, compared with other control formulations, including "immature" DC-MVs obtained without the MPLA pretreatment. Taken together, these results suggest that DC-MVs are an effective delivery platform for T cell activation and may serve as a potential delivery system for improving adoptive T cell therapy.
细胞膜最近作为一种很有前途的药物输送系统引起了关注。在这里，树突状细胞膜泡 (DC-MVs) 被用作促进 T 细胞反应的平台进行研究。纳米尺寸的 DC-MVs 是从用单磷酰脂质 A (MPLA)预处理的 DC 中衍生而来的，MPLA 是一种获得 FDA 批准的免疫刺激佐剂。这些“成熟”的 DC-MVs 在体外激活 DC，并增加其共刺激标志物的表达。DC-MVs 还促进体外抗原特异性 T 细胞的交叉呈递，增加其存活和 CD25 的表达。此外，与其他对照制剂相比，这些成熟的 DC-MVs 能够有效地增强体内过继转移的 CD8+T 细胞的扩增，产生的抗原特异性 T 细胞频率是其他对照制剂的两倍至四倍，包括未经 MPLA 预处理获得的“不成熟”DC-MVs。总之，这些结果表明 DC-MVs 是一种有效的 T 细胞激活的递药平台，并且可能作为改善过继性 T 细胞治疗的潜在递药系统。
