Evidence map›Paper›PMID 21343872›Full record

ArticleTransplantation2011

Antagonistic and agonistic anti-canine CD28 monoclonal antibodies: tools for allogeneic transplantation.

Scott S Graves, Diane M Stone, Carol Loretz, Laura J Peterson, Marina Lesnikova, Billanna Hwang, George E Georges, Richard Nash, Rainer Storb

Erratum issuedAbstract read
In one paragraph

Article in Transplantation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
0.9field-weighted citation impact, top 28% 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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
  2. A review of CD4Veterinary immunology and immunopathology · 2024
    Review
  3. Article
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  5. Review
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  18. Review
  19. Nonhuman primate transplant models finally evolve: detailed immunogenetic analysis creates new models and strengthens the old.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2012
    Review
  20. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Scott S GravesTransplantation Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA. sgraves@fhcrc.org
Diane M Stone
Carol Loretz
Laura J Peterson
Marina Lesnikova
Billanna Hwang
George E Georges
Richard Nash
Rainer Storb
Fred Hutch Cancer Center · USUniversity of Washington · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZA

Funding

Translational Bioimaging Core Shared ResourceP30CA015704 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI Eric Collisson · 1985 to 2026
$296.4M
Project 3: Stem Cell Allografts for Lymphoid MalignanciesP01CA078902 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SANDMAIER, BRENDA MARIE · 1999 to 2025
$46.1M
Transplantation of cord bloodU19AI067770 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEORGES, GEORGE EARL · 2005 to 2010
$23.2M
NCI NIH HHS P01 CA078902NCI NIH HHS P01CA078902NCI NIH HHS P30 CA015704NCI NIH HHS P30CA015704NIAID NIH HHS U19 AI067770NIAID NIH HHS U19AI067770
6 · The paper itself

Abstract

backgroundIt has been presumed that antibody-mediated selective costimulatory molecule blockade of CD28 is superior to cytotoxic T lymphocyte antigen 4 (CTLA4)-Ig. This is based on the premise that specifically blocking CD28 allows inhibitory signals through CTLA-4 to proceed, which furthermore suppresses T-cell function.

methodsThe extracelluar domain of canine (ca)CD28 was cloned from dog peripheral blood mononuclear cells. Mice were immunized with a caCD28/murine IgG2a fusion protein. Hybridomas were produced by fusing splenocytes with mouse NSO cells and screened for caCD28 binding by ELISA. Agonistic and antagonistic activities of the monoclonal antibodies (mAb) were tested in mixed leukocyte reactions. Canine regulatory T cells were expanded using plate-bound anti-CD3 and an anti-CD28 agonist mAb.

resultsOne agonistic and seven antagonistic mAbs to canine (ca)CD28 were cloned. Binding studies indicated that an agonistic (5B8) and an antagonistic (1C6) mAb bound equally well to a caCD28/caIgG1 fusion protein and to CD28 expressed on CD4+ and CD8+ peripheral blood T cells. Antagonistic antibody blocked mixed lymphocyte reactions (MLR) in a dose-dependent manner similar to CTLA4-Ig, whereas the agonistic antibody to caCD28 enhanced MLR. The 5B8 was superior to 1C6 when either was combined with anti-caCD3 to stimulate lymphocyte proliferation. Furthermore, the agonistic mAb, 5B8, together with anti-CD3 mAb induced 100-fold proliferation of canine regulatory T cells. Relative to untreated control cells, anti-caCD28 (1C6) and CTLA4-Ig equivalently inhibited cytotoxic T lymphocyte-mediated killing of alloreactive target cells.

conclusionThese studies demonstrated that mouse anti-caCD28 mAbs can be generated with agonistic or antagonistic function.

Indexed as

AnimalsAntibodies, MonoclonalAntigens, CDBinding Sites, AntibodyCD28 AntigensCell ProliferationCTLA-4 AntigenDogsDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayGraft RejectionHybridomasLymphocyte ActivationLymphocyte Culture Test, MixedMiceOrgan TransplantationAntibodies, MonoclonalAntigens, CDCD28 AntigensCTLA-4 AntigenCtla4 protein, mouseRecombinant Fusion Proteins

Identifiers

PMID21343872
PMCPMC3180996
OpenAlexW2056510701

What OpenQuestion holds

Textmetadata
LicenceTDM
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.