期刊
NATURE BIOTECHNOLOGY
卷 36, 期 2, 页码 160-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.4047
关键词
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资金
- National Institutes of Health (NIH) [1R01EB015498 U01 CA214369]
- Wyss Institute for Biologically Inspired Engineering at Harvard University
- Canadian Institutes of Health Research (CIHR-DFSA)
- HHMI ISRF
- National Science Foundation under NSF [1541959]
- NIH [UL1 TR001102]
Therapeutic ex vivo T-cell expansion is limited by low rates and T-cell products of limited functionality. Here we describe a system that mimics natural antigen-presenting cells (APCs) and consists of a fluid lipid bilayer supported by mesoporous silica micro-rods. The lipid bilayer presents membrane-bound cues for T-cell receptor stimulation and costimulation, while the microrods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APCmimetic scaffolds (APC-ms) promote two-to tenfold greater polyclonal expansion of primary mouse and human T cells compared with commercial expansion beads (Dynabeads). The efficiency of expansion depends on the density of stimulatory cues and the amount of material in the starting culture. Following a single stimulation, APC-ms enables antigen-specific expansion of rare cytotoxic T-cell subpopulations at a greater magnitude than autologous monocyte-derived dendritic cells after 2 weeks. APC-ms support over fivefold greater expansion of restimulated CD19 CAR-T cells than Dynabeads, with similar efficacy in a xenograft lymphoma model.
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