Evidence map›Paper›PMID 30753169›Full record

ArticleJCI insight2019

Systematic testing and specificity mapping of alloantigen-specific chimeric antigen receptors in regulatory T cells.

Nicholas Aj Dawson, Caroline Lamarche, Romy E Hoeppli, Peter Bergqvist, Vivian Cw Fung, Emma McIver, Qing Huang, Jana Gillies, Madeleine Speck, Paul C Orban and 3 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
5.9field-weighted citation impact, top 3% 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

77 citing papers in PubMed, 92 citations in OpenAlex.

  1. Regulatory T cells: From Foxp3 to tolerance-inducing therapies.The Journal of investigative dermatology · 2026
    Review
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  12. Armored human CAR TScience advances · 2025
    Article
  13. Article
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  16. Immunometabolism of Liver Xenotransplantation and Prospective Solutions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  17. Unlocking Transplant Tolerance with Biomaterials.Advanced healthcare materials · 2025
    Review
  18. Review
  19. Review
  20. Review

17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Nicholas Aj DawsonDepartment of Medicine and.
Caroline LamarcheDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Romy E HoeppliDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Peter BergqvistCentre for Drug and Research and Development, Vancouver, British Columbia, Canada.
Vivian Cw FungDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Emma McIverDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Qing HuangDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Jana GilliesDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Madeleine SpeckDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Paul C OrbanDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Jonathan W BushBC Children's Hospital Research Institute (BCCHR), Vancouver, British Columbia, Canada.
Majid MojibianDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
Megan K LevingsDepartment of Surgery, University of British Columbia (UBC), Vancouver, British Columbia, Canada.
University of British Columbia · CABC Children's Hospital · CACentre for Drug Research and Development · CAUniversity of British Columbia Hospital · CA

Funding

CIHR FDN-154304
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) technology can be used to engineer the antigen specificity of regulatory T cells (Tregs) and improve their potency as an adoptive cell therapy in multiple disease models. As synthetic receptors, CARs carry the risk of immunogenicity, particularly when derived from nonhuman antibodies. Using an HLA-A*02:01-specific CAR (A2-CAR) encoding a single-chain variable fragment (Fv) derived from a mouse antibody, we developed a panel of 20 humanized A2-CARs (hA2-CARs). Systematic testing demonstrated variations in expression, and ability to bind HLA-A*02:01 and stimulate human Treg suppression in vitro. In addition, we developed a new method to comprehensively map the alloantigen specificity of CARs, revealing that humanization reduced HLA-A cross-reactivity. In vivo bioluminescence imaging showed rapid trafficking and persistence of hA2-CAR Tregs in A2-expressing allografts, with eventual migration to draining lymph nodes. Adoptive transfer of hA2-CAR Tregs suppressed HLA-A2+ cell-mediated xenogeneic graft-versus-host disease and diminished rejection of human HLA-A2+ skin allografts. These data provide a platform for systematic development and specificity testing of humanized alloantigen-specific CARs that can be used to engineer specificity and homing of therapeutic Tregs.

Indexed as

Adoptive TransferAllograftsAnimalsFemaleHLA-A2 AntigenHLA-A AntigensHumansImmune ToleranceImmunotherapyImmunotherapy, AdoptiveIsoantigensK562 CellsMiceMice, TransgenicReceptors, Chimeric AntigenSingle-Chain AntibodiesHLA-A2 AntigenHLA-A AntigensIsoantigensReceptors, Chimeric AntigenSingle-Chain AntibodiesImmunologyImmunotherapyOrgan transplantationToleranceTransplantation

Identifiers

PMID30753169
PMCPMC6483008
OpenAlexW2913828923

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.