Evidence map›Paper›PMID 28985411›Full record

ArticleProtein engineering, design & selection : PEDS2017

Tethered-variable CL bispecific IgG: an antibody platform for rapid bispecific antibody screening.

Hok Seon Kim, Diana Ronai Dunshee, Angie Yee, Raymond K Tong, Ingrid Kim, Farzam Farahi, Jo-Anne Hongo, James A Ernst, Junichiro Sonoda, Christoph Spiess

Open access · bronzeAbstract read
In one paragraph

Article in Protein engineering, design & selection : PEDS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 23% 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, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. 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

10 authors.

Hok Seon KimDepartment of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Diana Ronai DunsheeDepartment of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Angie YeeDepartment of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Raymond K TongDepartment of Protein Chemistry, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Ingrid KimDepartment of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Farzam FarahiDepartment of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Jo-Anne HongoDepartment of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
James A ErnstDepartment of Protein Chemistry, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Junichiro SonodaDepartment of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Christoph SpiessDepartment of Antibody Engineering, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bispecific antibodies offer a clinically validated platform for drug discovery. In generating functionally active bispecific antibodies, it is necessary to identify a unique parental antibody pair to merge into a single molecule. However, technologies that allow high-throughput production of bispecific immunoglobulin Gs (BsIgGs) for screening purposes are limited. Here, we describe a novel bispecific antibody format termed tethered-variable CLBsIgG (tcBsIgG) that allows robust production of intact BsIgG in a single cell line, concurrently ensuring cognate light chain pairing and preserving key antibody structural and functional properties. This technology is broadly applicable in the generation of BsIgG from a variety of antibody isotypes, including human BsIgG1, BsIgG2 and BsIgG4. The practicality of the tcBsIgG platform is demonstrated by screening BsIgGs generated from FGF21-mimetic anti-Klotho-β agonistic antibodies in a combinatorial manner. This screen identified multiple biepitopic combinations with enhanced agonistic activity relative to the parental monoclonal antibodies, thereby demonstrating that biepitopic antibodies can acquire enhanced functionality compared to monospecific parental antibodies. By design, the tcBsIgG format is amenable to high-throughput production of large panels of bispecific antibodies and thus can facilitate the identification of rare BsIgG combinations to enable the discovery of molecules with improved biological function.

Indexed as

High-Throughput Screening AssaysAnimalsAntibodies, BispecificAntibodies, MonoclonalCHO CellsCloning, MolecularCricetulusFibroblast Growth FactorsGene ExpressionGenetic VectorsHEK293 CellsHumansImmunoglobulin GKlotho ProteinsMembrane ProteinsMiceAntibodies, BispecificAntibodies, MonoclonalFGFR1 protein, humanfibroblast growth factor 21Fibroblast Growth FactorsImmunoglobulin GKLB protein, humanKlotho ProteinsMembrane ProteinsReceptor, Fibroblast Growth Factor, Type 1Recombinant Proteinsbiepitopic antibodybispecific antibodyFGF21FGFR1high throughput screeningKLBtherapeutic mAb

Identifiers

PMID28985411
PMCPMC5914367
OpenAlexW2731954367

What OpenQuestion holds

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LicenceCC BY-NC
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.