Evidence map›Paper›PMID 25988188›Full record

ArticleTransplantation direct2015

Anti-CD28 Antibody-Initiated Cytokine Storm in Canines.

Steven L Rosinski, Rainer Storb, Roland K Strong, George E Sale, Diane M Stone, Mesfin M Gewe, Della J Friend, V Kraig Abrams, Julie Randolph-Habecker, Scott S Graves

Open access · goldAbstract read
In one paragraph

Article in Transplantation direct, 2015. 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
1.9field-weighted citation impact, top 14% 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, 24 citations in OpenAlex.

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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 2 institutions in 1 country.

Steven L RosinskiClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109 ; Department of Medicine, University of Washington, Seattle, Washington, 98195.
Rainer StorbClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109 ; Department of Medicine, University of Washington, Seattle, Washington, 98195.
Roland K StrongBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
George E SaleClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
Diane M StoneClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
Mesfin M GeweBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
Della J FriendBasic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
V Kraig AbramsClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
Julie Randolph-HabeckerComparative Medicine, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109.
Scott S GravesClinical Research Division, Fred Hutchinson Cancer Research Center, Seattle Washington, 98109 ; Department of Medicine, University of Washington, Seattle, Washington, 98195.
Fred Hutch Cancer Center · USUniversity of Washington · US

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
B7-based, CD28 or CTLA-4-specific agonists and antagonists for tolerance inductioR21AI097786 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STRONG, ROLAND K · 2012 to 2013
$469k
Characterization of Chronic Graft-Versus-Host Disease in the Canine ModelR21OD010489 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GRAVES, SCOTT STOLL · 2013 to 2014
$460k
NCI NIH HHS P01 CA078902NCI NIH HHS P30 CA015704NIAID NIH HHS R21 AI097786NIH HHS R21 OD010489
6 · The paper itself

Abstract

backgroundCD28 signal blockade following T cell receptor activation is under intense investigation as a tolerance-inducing therapy for transplantation. Our goal is to produce a CD28-specific reagent as a therapy for the prevention of graft rejection and graft-versus-host disease in the canine model of allogeneic hematopoietic cell transplantation (HCT).

methodsWe infused a monoclonal mouse anti-canine CD28 antibody (1C6 mAb) into four dogs and a fragment of antigen-binding (1C6 Fab) into two dogs. Pharmacokinetics, pathology, cytokine release, and the crystal structure of 1C6 Fv were evaluated.

resultsWithin an hour of an IV injection of the 1C6 mAb, the dogs became leukopenic and developed a steroid-refractory cytokine storm. Two of the dogs developed high fevers, one experienced diffuse alveolar hemorrhage, and another developed gastrointestinal hemorrhage. The cytokine storm was characterized by elevated plasma levels of MCP-1, IP-10, IL-10, IL-6, and TNF-α. In addition, one dog showed elevated levels of IL-2, IL-8, and IL-18. In contrast, infusion of 1C6 Fab was well tolerated without any side effects. Dry-coating 1C6 mAb onto tissue culture plates induced CD3-independent proliferation and TNF-alpha production. Crystal structure analysis revealed that 1C6 binds to canine CD28 in a manner different than previously reported for conventional agonistic or superagonistic antibodies.

conclusionsThese results indicate that dogs and humans develop a similar cytokine storm following infusion ofanti-CD28 mAb, providing an appropriate large animal for further study. 1C6 Fab warrants evaluation as a tolerance-inducing reagent in the canine model of allogeneic HCT.

Identifiers

PMID25988188
PMCPMC4433175
OpenAlexW2076564879

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.