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Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells
Open accessAbstract
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.
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Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
Maude, S. L., Frey, N., Shaw, P. A., Aplenc, R., Barrett, D. M., Bunin, N. J., Chew, A., Gonzalez, V. E., Zheng, Z., Lacey, S. F., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1407222 · Cited by 5,413
Lee, D. W., Kochenderfer, J. N., Stetler-Stevenson, M., Cui, Y. K., Delbrook, C., Feldman, S. A., Fry, T. J., Orentas, R., Sabatino, M., Shah, N. N., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61403-3 · Cited by 2,898
CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients
Turtle, C. J., Hanafi, L.-A., Berger, C., Gooley, T. A., Cherian, S., Hudecek, M., Sommermeyer, D., Melville, K., Pender, B., Budiarto, T. M., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85309 · Cited by 2,112
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Goldberg, M. S. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0186-9 · Cited by 628
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Shields, C. W., Evans, M. A., Wang, L. L.-W., Baugh, N., Iyer, S., Wu, D., Zhao, Z., Pusuluri, A., Ukidve, A., Pan, D. C., et al. (2020) · Science Advances · doi:10.1126/sciadv.aaz6579 · Cited by 414
CAR-T cell manufacturing: Major process parameters and next-generation strategies
Ayala Ceja, M., Khericha, M., Harris, C. M., Puig-Saus, C., & Chen, Y. Y. (2024) · Journal of Experimental Medicine · doi:10.1084/jem.20230903 · Cited by 303
Li, J., & Kataoka, K. (2021) · Journal of the American Chemical Society · doi:10.1021/jacs.0c09029 · Cited by 281
Metadata
- Authors
- Cheung, A. S., Zhang, D. K. Y., Koshy, S. T., & Mooney, D. J.
- Venue
- Nature Biotechnology
- Published
- 2018-01-15
- Volume
- 36
- Issue
- 2
- Pages
- 160-169
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2783878221
- Cited by
- 372
- References
- 3
- FWCI
- 14.04
- Type
- journal article
- Language
- en
- Open access
- green
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- Cheung, A. S., Zhang, D. K. Y., Koshy, S. T., & Mooney, D. J. (2018). Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells. Nature Biotechnology. https://doi.org/10.1038/nbt.4047
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