Evidence map›Paper›PMID 23635093›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2013

Ex vivo-expanded cynomolgus macaque regulatory T cells are resistant to alemtuzumab-mediated cytotoxicity.

E M Dons, G Raimondi, H Zhang, A F Zahorchak, J K Bhama, L Lu, M Ezzelarab, J N M Ijzermans, D K C Cooper, A W Thomson

Open access · bronzeAbstract read
In one paragraph

Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. A method for expansion of T cells from cynomolgus monkey (Macaca fascicularis).In vitro cellular & developmental biology. Animal · 2018
    Article
  4. Article
  5. Review
  6. Regulatory T Cell Infusion Can Enhance Memory T Cell and Alloantibody Responses in Lymphodepleted Nonhuman Primate Heart Allograft Recipients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2016
    Article
  7. Article
  8. Sequential monitoring and stability of ex vivo-expanded autologous and nonautologous regulatory T cells following infusion in nonhuman primates.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2015
    Article
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

10 authors at 3 institutions in 2 countries.

E M DonsDepartment of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
G Raimondi
H Zhang
A F Zahorchak
J K Bhama
L Lu
M Ezzelarab
J N M Ijzermans
D K C Cooper
A W Thomson
University of Pittsburgh · USErasmus MC · NLUniversity of Pittsburgh Medical Center · US

Funding

University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Alemtuzumab and Regulatory T Cells for Heart Transplant Tolerance in MonkeysU01AI091197 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI THOMSON, ANGUS W · 2010 to 2016
$4.3M
NCATS NIH HHS UL1 TR000005NIAID NIH HHS U01 AI091197NIAID NIH HHS U01-AI091197
6 · The paper itself

Abstract

Alemtuzumab (Campath-1H) is a humanized monoclonal antibody (Ab) directed against CD52 that depletes lymphocytes and other leukocytes, mainly by complement-dependent mechanisms. We investigated the influence of alemtuzumab (i) on ex vivo-expanded cynomolgus monkey regulatory T cells (Treg) generated for prospective use in adoptive cell therapy and (ii) on naturally occurring Treg following alemtuzumab infusion. Treg were isolated from PBMC and lymph nodes and expanded for two rounds. CD52 expression, binding of alemtuzumab and both complement-mediated killing and Ab-dependent cell-mediated cytotoxicity (ADCC) were compared between freshly isolated and expanded Treg and effector T cells. Monkeys undergoing allogeneic heart transplantation given alemtuzumab were monitored for Treg and serum alemtuzumab activity. Ex vivo-expanded Treg showed progressive downregulation of CD52 expression, absence of alemtuzumab binding, minimal change in complement inhibitory protein (CD46) expression and no complement-dependent killing or ADCC. Infusion of alemtuzumab caused potent depletion of all lymphocytes, but a transient increase in the incidence of circulating Treg. After infusion of alemtuzumab, monkey serum killed fresh PBMC, but not expanded Treg. Thus, expanded cynomolgus monkey Treg are resistant to alemtuzumab-mediated, complement-dependent cytotoxicity. Furthermore, our data suggest that these expanded monkey Treg can be infused into graft recipients given alemtuzumab without risk of complement-mediated killing.

Indexed as

Antibody-Dependent Cell CytotoxicityAlemtuzumabAnimalsAntibodies, Monoclonal, HumanizedAntibodies, NeoplasmAntigens, CDAntigens, NeoplasmAntineoplastic AgentsCD52 AntigenErythrocytesGlycoproteinsLeukocytes, MononuclearMacaca fascicularisT-Lymphocytes, RegulatoryAlemtuzumabAntibodies, Monoclonal, HumanizedAntibodies, NeoplasmAntigens, CDAntigens, NeoplasmAntineoplastic AgentsCD52 AntigenGlycoproteinsAlemtuzumabCampath-1Hnonhuman primateregulatory T cellstransplantation

Identifiers

PMID23635093
PMCPMC3780590
OpenAlexW1922135726

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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.