The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor
Open accessAbstract
Adoptive immunotherapy with regulatory T cells (Tregs) is a promising treatment for allograft rejection and graft-versus-host disease (GVHD). Emerging data indicate that, compared with polyclonal Tregs, disease-relevant antigen-specific Tregs may have numerous advantages, such as a need for fewer cells and reduced risk of nonspecific immune suppression. Current methods to generate alloantigen-specific Tregs rely on expansion with allogeneic antigen-presenting cells, which requires access to donor and recipient cells and multiple MHC mismatches. The successful use of chimeric antigen receptors (CARs) for the generation of antigen-specific effector T cells suggests that a similar approach could be used to generate alloantigen-specific Tregs. Here, we have described the creation of an HLA-A2-specific CAR (A2-CAR) and its application in the generation of alloantigen-specific human Tregs. In vitro, A2-CAR-expressing Tregs maintained their expected phenotype and suppressive function before, during, and after A2-CAR-mediated stimulation. In mouse models, human A2-CAR-expressing Tregs were superior to Tregs expressing an irrelevant CAR at preventing xenogeneic GVHD caused by HLA-A2+ T cells. Together, our results demonstrate that use of CAR technology to generate potent, functional, and stable alloantigen-specific human Tregs markedly enhances their therapeutic potential in transplantation and sets the stage for using this approach for making antigen-specific Tregs for therapy of multiple diseases.
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Cites
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Self-citation
Research works printed but not linked: 3
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Cited by
Regulatory T Cells and Human Disease
Sakaguchi, S., Mikami, N., Wing, J. B., Tanaka, A., Ichiyama, K., & Ohkura, N. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041717 · Cited by 1,120
Treg cell-based therapies: challenges and perspectives
Raffin, C., Vo, L. T., & Bluestone, J. A. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0232-6 · Cited by 720
CAR immune cells: design principles, resistance and the next generation
Labanieh, L., & Mackall, C. L. (2023) · Nature · doi:10.1038/s41586-023-05707-3 · Cited by 658
Kasperkiewicz, M., Ellebrecht, C. T., Takahashi, H., Yamagami, J., Zillikens, D., Payne, A. S., & Amagai, M. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.26 · Cited by 523
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Metadata
- Authors
- MacDonald, K. G., Hoeppli, R. E., Huang, Q., Gillies, J., Luciani, D. S., Orban, P. C., Broady, R., & Levings, M. K.
- Venue
- Journal of Clinical Investigation
- Published
- 2016-03-21
- Volume
- 126
- Issue
- 4
- Pages
- 1413-1424
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2303852857
- Cited by
- 494
- References
- 61
- FWCI
- 24.40
- Type
- journal article
- Language
- en
- Open access
- bronze
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