Evidence map›Paper›PMID 33755713›Full record

Trial reportPloS one2021

Characterization of the robust humoral immune response to GSK2618960, a humanized anti-IL-7 receptor monoclonal antibody, observed in healthy subjects in a Phase 1 study.

Karen Liao, Keguan Chen, Sara Brett, Andrew Gehman, Ann M Schwartz, George R Gunn, Stephen L DeWall

Open access · goldAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 41% 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

6 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
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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

7 authors at 1 institution in 1 country.

Karen LiaoImmunogenicity Group, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.ORCID 0000-0002-4685-7179
Keguan ChenImmunogenicity Group, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
Sara BrettOncology Cell Therapy, Oncology R&D, Stevenage, United Kingdom.
Andrew GehmanResearch Statistics, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
Ann M SchwartzImmunogenicity Group, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
George R GunnImmunogenicity Group, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
Stephen L DeWallImmunogenicity Group, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
GlaxoSmithKline (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Interleukin-7 (IL-7) signaling modulates T cell activity and is implicated in numerous autoimmune diseases. An anti-IL-7 receptor monoclonal antibody (GSK2618960) biotherapeutic was evaluated in healthy subjects for safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity in a single-dose escalation phase I study. We found that antibodies against GSK2618960 (i.e., anti-drug antibodies or ADA) developed in 83% and 100% of GSK2618960-treated subjects in the 0.6 and 2.0 mg/kg dose cohorts, respectively. Of the ADA positive subjects, 64% (7 of 11) had detectable neutralizing activity. Further investigation revealed the presence of GSK2618960-specific memory B cells, indicating the development of immunological memory for the ADAs. Ex vivo stimulation of peripheral blood mononuclear cell (PBMC) samples demonstrated a relatively strong CD4+ T cell proliferation response to GSK2618960 as compared to the control anti-RSV antibody (which is known to have only low immunogenic potential), confirming the high immunogenic potential of GSK2618960. Furthermore, GSK2618960 was found to bind in vitro monocyte-derived dendritic cells (DCs). GSK2618960 treatment of PBMCs increased the proportion of DC cells showing an increase in expression of CD83, CD86 and CD209, which indicated enhanced DC differentiation and activation relative to the isotype control anti-β amyloid antibody. Collectively, the evidence supports that the high incidence of observed clinical immunogenicity was likely related to the receptor-mediated activity by GSK2618960.

Indexed as

Immunity, HumoralAntibodies, Monoclonal, HumanizedAutoantibodiesAutoimmune DiseasesB-LymphocytesCD4-Positive T-LymphocytesDendritic CellsDouble-Blind MethodHealthy VolunteersHumansLeukocytes, MononuclearPlacebo EffectReceptors, Interleukin-7Antibodies, Monoclonal, HumanizedAutoantibodiesGSK2618960Receptors, Interleukin-7

Identifiers

PMID33755713
PMCPMC7987154
OpenAlexW3135985525

What Socratic holds

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LicenceCC BY
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Registered trials

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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 Socratic graph.