Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T-cells
Abstrak
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 micro-rods enable sustained release of soluble paracrine cues. Using anti-CD3, anti-CD28, and interleukin-2, we show that the APC-mimetic 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.
Penulis (4)
Alexander S Cheung
David K. Y. Zhang
Sandeep T. Koshy
D. Mooney
Akses Cepat
- Tahun Terbit
- 2017
- Bahasa
- en
- Total Sitasi
- 328×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1038/nbt.4047
- Akses
- Open Access ✓