Evidence map›Paper›PMID 26999600›Full record

ArticleThe Journal of clinical investigation2016

Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor.

Katherine G MacDonald, Romy E Hoeppli, Qing Huang, Jana Gillies, Dan S Luciani, Paul C Orban, Raewyn Broady, Megan K Levings

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 303 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
303citing papers in PubMed, 1 pooled it
22.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

303 citing papers in PubMed, 1 synthesis or guideline pooled it, 462 citations in OpenAlex.

  1. Pooled it
  2. Regulatory T cells: From Foxp3 to tolerance-inducing therapies.The Journal of investigative dermatology · 2026
    Review
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  11. Engineering CAR-Tregs with Phage-Selected scFv Enables a New Paradigm for Immune Regulation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  12. Article
  13. Induction of Clinical Operational Tolerance Through Immunosuppression Minimization: Less Is More?Liver international : official journal of the International Association for the Study of the Liver · 2026
    Review
  14. CAR-mediated release of IL-10 increases the function of regulatory T cells: Relevance for future clinical application.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  15. Review
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243 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Katherine G MacDonald
Romy E Hoeppli
Qing Huang
Jana Gillies
Dan S Luciani
Paul C Orban
Raewyn Broady
Megan K Levings
Child and Family Research Institute · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

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.

Indexed as

Receptors, Antigen, T-CellRecombinant Fusion ProteinsAnimalsFemaleHLA-A2 AntigenHumansIsoantigensMaleMiceT-Lymphocytes, RegulatoryHLA-A2 AntigenIsoantigensReceptors, Antigen, T-CellRecombinant Fusion Proteins

Identifiers

PMID26999600
PMCPMC4811124
OpenAlexW2303852857

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.