Evidence map›Paper›PMID 26458513›Full record

ArticleTransplant immunology2015

In vitro testing of an anti-CD40 monoclonal antibody, clone 2C10, in primates and pigs.

Whayoung Lee, Vikas Satyananda, Hayato Iwase, Takayuki Tanaka, Yuko Miyagawa, Cassandra Long, David Ayares, David K C Cooper, Hidetaka Hara

Open access · greenAbstract readComparative Study
In one paragraph

Article in Transplant immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. 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

9 authors at 1 institution in 1 country.

Whayoung LeeThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Vikas SatyanandaThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Hayato IwaseThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Takayuki TanakaThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Yuko MiyagawaThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Cassandra LongThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
David AyaresRevivicor, Blacksburg, VA, USA.
David K C CooperThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Hidetaka HaraThomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: harah@upmc.edu.
University of Pittsburgh · US

Funding

Prolonging life-supported pig kidney and heart graft survival in baboons by suppressing inflammationU19AI090959 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2010 to 2024
$26.3M
Therapeutic assessment of synthetic heparin sulfates in transplantation modelsP01HL107152 · NHLBI · VIRGINIA COMMONWEALTH UNIVERSITY · PI DESAI, UMESH RAMANLAL · 2011 to 2017
$15.8M
Thromboregulation to Prevent Thrombotic MicroangiopathyU01AI068642 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2005 to 2008
$2.7M
Tolerance to Carbohydrate Antigens in TransplantationR21AI074844 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI COOPER, DAVID KC · 2007 to 2008
$405k
NHLBI NIH HHS 1P01 HL107152NHLBI NIH HHS P01 HL107152NIAID NIH HHS HHSN272201300031CNIAID NIH HHS R21 AI074844NIAID NIH HHS U01 AI068642NIAID NIH HHS U19 AI090959NIAID NIH HHS U19 AI090959-01PHS HHS HHNS272200130031CPHS HHS R21 A1074844
6 · The paper itself

Abstract

backgroundThe CD40/CD154 and CD28/B7 pathways are important in allo- and xeno-transplantation. Owing to the thrombotic complications of anti-CD154mAb, anti-CD40mAb has emerged as a promising inhibitor of costimulation. Various clones of anti-CD40mAb have been developed against primate species, e.g., clone 2C10 against rhesus monkeys. We have compared the in vitro efficacy of 2C10 to prevent a T cell response in primates and pigs.

methodsThe binding of 2C10 to antigen-presenting cells (PBMCs [B cells]) of humans, rhesus and cynomolgus monkeys, baboons, and pigs was measured by flow cytometry, and was also tested indirectly by a blocking assay. The functional capacity of 2C10 was tested by mixed lymphocyte reaction (MLR) with polyclonal stimulation by phytohemagglutinin (PHA) and also with wild-type pig aortic endothelial cells (pAECs) as stimulators.

resultsThere was a significant reduction in binding of 2C10 to baboon PBMCs compared to rhesus, cynomolgus, and human PBMCs, and minimal binding to pig PBMCs. The blocking assay confirmed that the binding of 2C10 was significantly lower to baboon PBMCs when compared to the other primate species tested. The functional assay with PHA showed significantly reduced inhibition of PBMC proliferation in humans, cynomolgus monkeys, and baboons compared to rhesus monkeys, which was confirmed on MLR with pAECs.

conclusionsSince both the binding and functional activity of 2C10 in the baboon is lower than in rhesus monkeys, in vivo treatment using 2C10 in the baboon might require a higher dose or more frequent administration in comparison to rhesus monkeys. It may also be beneficial to develop species-specific clones of anti-CD40mAb.

Indexed as

AnimalsAntibodies, MonoclonalB-LymphocytesCD40 AntigensCell ProliferationCells, CulturedCoculture TechniquesDisease Models, AnimalEndothelium, VascularGraft RejectionHumansLymphocyte Culture Test, MixedPrimatesSwineT-LymphocytesAntibodies, MonoclonalCD40 AntigensAnti-CD40 monoclonal antibodyCostimulation blockadeNonhuman primatePigTransplantationXenotransplantation

Identifiers

PMID26458513
PMCPMC4648655
OpenAlexW2158325125

What OpenQuestion holds

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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.