Evidence map›Paper›PMID 25467949›Full record

ReviewArchivum immunologiae et therapiae experimentalis2015

Human antibody production in transgenic animals.

Marianne Brüggemann, Michael J Osborn, Biao Ma, Jasvinder Hayre, Suzanne Avis, Brian Lundstrom, Roland Buelow

Open access · hybridAbstract readReview
In one paragraph

Review in Archivum immunologiae et therapiae experimentalis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
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  12. Molecular Farming of Pembrolizumab and Nivolumab.International journal of molecular sciences · 2023
    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.

Marianne BrüggemannRecombinant Antibody Technology Ltd., Babraham Research Campus, Babraham, Cambridge, CB22 3AT, UK, mbruggemann@ratltd.net.
Michael J Osborn
Biao Ma
Jasvinder Hayre
Suzanne Avis
Brian Lundstrom
Roland Buelow
Recombinant Antibody Technology (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fully human antibodies from transgenic animals account for an increasing number of new therapeutics. After immunization, diverse human monoclonal antibodies of high affinity can be obtained from transgenic rodents, while large animals, such as transchromosomic cattle, have produced respectable amounts of specific human immunoglobulin (Ig) in serum. Several strategies to derive animals expressing human antibody repertoires have been successful. In rodents, gene loci on bacterial artificial chromosomes or yeast artificial chromosomes were integrated by oocyte microinjection or transfection of embryonic stem (ES) cells, while ruminants were derived from manipulated fibroblasts with integrated human chromosome fragments or human artificial chromosomes. In all strains, the endogenous Ig loci have been silenced by gene targeting, either in ES or fibroblast cells, or by zinc finger technology via DNA microinjection; this was essential for optimal production. However, comparisons showed that fully human antibodies were not as efficiently produced as wild-type Ig. This suboptimal performance, with respect to immune response and antibody yield, was attributed to imperfect interaction of the human constant region with endogenous signaling components such as the Igα/β in mouse, rat or cattle. Significant improvements were obtained when the human V-region genes were linked to the endogenous CH-region, either on large constructs or, separately, by site-specific integration, which could also silence the endogenous Ig locus by gene replacement or inversion. In animals with knocked-out endogenous Ig loci and integrated large IgH loci, containing many human Vs, all D and all J segments linked to endogenous C genes, highly diverse human antibody production similar to normal animals was obtained.

Indexed as

ImmunotherapyAnimalsAnimals, Genetically ModifiedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCattleFibroblastsHumansImmunoglobulin Constant RegionsMiceMicroinjectionsOocytesProtein EngineeringRatsSpecies SpecificityAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedImmunoglobulin Constant Regions

Identifiers

PMID25467949
PMCPMC4359279
OpenAlexW2091532444

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.