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Cited by 494

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 access
MacDonald, Katherine G., Hoeppli, Romy E., Huang, Qing, Gillies, Jana, Luciani, Dan S., Orban, Paul C., Broady, Raewyn, Levings, Megan K.·2016·Journal of Clinical Investigation

Abstract

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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Research works printed but not linked: 3

  1. 10.1034/j.1399-0039.2000.550108.x · doi:10.1034/j.1399-0039.2000.550108.x
  2. 10.1111/j.1399-0039.1994.tb02363.x · doi:10.1111/j.1399-0039.1994.tb02363.x
  3. 10.1038/nm0103-4 · doi:10.1038/nm0103-4

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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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CoChat. (2026). Citation check: Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. https://app.cochat.ai/papers/10.1172/jci82771
The paper
MacDonald, K. G., Hoeppli, R. E., Huang, Q., Gillies, J., Luciani, D. S., Orban, P. C., Broady, R., & Levings, M. K. (2016). Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. Journal of Clinical Investigation. https://doi.org/10.1172/jci82771

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