Evidence map›Paper›PMID 28559564›Full record

ArticleScientific reports2017

Efficient Generation of Bispecific Murine Antibodies for Pre-Clinical Investigations in Syngeneic Rodent Models.

Aran F Labrijn, Joyce I Meesters, Matthew Bunce, Anthony A Armstrong, Sandeep Somani, Tom C Nesspor, Mark L Chiu, Işil Altintaş, Sandra Verploegen, Janine Schuurman and 1 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 42 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

11 authors at 3 institutions in 3 countries.

Aran F LabrijnGenmab, Utrecht, The Netherlands.ORCID 0000-0001-9239-8439
Joyce I MeestersGenmab, Utrecht, The Netherlands.ORCID 0000-0002-3937-7601
Matthew BunceBiologics Research, Janssen Research and Development, LLC., Spring House, PA, USA.
Anthony A ArmstrongBiologics Research, Janssen Research and Development, LLC., Spring House, PA, USA.
Sandeep SomaniDiscovery Sciences, Janssen Research and Development, LLC., Spring House, PA, USA.
Tom C NessporBiologics Research, Janssen Research and Development, LLC., Spring House, PA, USA.
Mark L ChiuBiologics Research, Janssen Research and Development, LLC., Spring House, PA, USA.
Işil AltintaşGenmab, Utrecht, The Netherlands.
Sandra VerploegenGenmab, Utrecht, The Netherlands.
Janine SchuurmanGenmab, Utrecht, The Netherlands.ORCID 0000-0002-9738-9926
Paul W H I ParrenGenmab, Utrecht, The Netherlands. p.parren@genmab.com.ORCID 0000-0002-4365-3859
Genmab (Netherlands) · NLJanssen (United States) · USUniversity of Southern Denmark · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic concepts exploiting tumor-specific antibodies are often established in pre-clinical xenograft models using immuno-deficient mice. More complex therapeutic paradigms, however, warrant the use of immuno-competent mice, that more accurately capture the relevant biology that is being exploited. These models require the use of (surrogate) mouse or rat antibodies to enable optimal interactions with murine effector molecules. Immunogenicity is furthermore decreased, allowing longer-term treatment. We recently described controlled Fab-arm exchange (cFAE) as an easy-to-use method for the generation of therapeutic human IgG1 bispecific antibodies (bsAb). To facilitate the investigation of dual-targeting concepts in immuno-competent mice, we now applied and optimized our method for the generation of murine bsAbs. We show that the optimized combinations of matched point-mutations enabled efficient generation of murine bsAbs for all subclasses studied (mouse IgG1, IgG2a and IgG2b; rat IgG1, IgG2a, IgG2b, and IgG2c). The mutations did not adversely affect the inherent effector functions or pharmacokinetic properties of the corresponding subclasses. Thus, cFAE can be used to efficiently generate (surrogate) mouse or rat bsAbs for pre-clinical evaluation in immuno-competent rodents.

Indexed as

AnimalsAntibodies, BispecificHumansImmunoglobulin GMiceModels, AnimalNeoplasmsPoint MutationRatsXenograft Model Antitumor AssaysAntibodies, BispecificImmunoglobulin G

Identifiers

PMID28559564
PMCPMC5449386
OpenAlexW2617135370

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.