Evidence map›Paper›PMID 28981885›Full record

ArticleProtein engineering, design & selection : PEDS2017

Novel CH1:CL interfaces that enhance correct light chain pairing in heterodimeric bispecific antibodies.

Maximilian Bönisch, Carolin Sellmann, Daniel Maresch, Claudia Halbig, Stefan Becker, Lars Toleikis, Björn Hock, Florian Rüker

Abstract 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–field-weighted citation impact
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

28 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Review
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

8 authors.

Maximilian BönischChristian Doppler Laboratory for Antibody Engineering at Department of Chemistry and Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, A-1190 Vienna, Austria.
Carolin SellmannInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Straße 4, D-64287 Darmstadt, Germany.
Daniel MareschDepartment of Chemistry, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, A-1190 Vienna, Austria.
Claudia HalbigChristian Doppler Laboratory for Antibody Engineering at Department of Chemistry and Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, A-1190 Vienna, Austria.
Stefan BeckerProtein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Straße 250, D-64293 Darmstadt, Germany.
Lars ToleikisProtein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Straße 250, D-64293 Darmstadt, Germany.
Björn HockProtein Engineering and Antibody Technologies, Merck KGaA, Frankfurter Straße 250, D-64293 Darmstadt, Germany.
Florian RükerChristian Doppler Laboratory for Antibody Engineering at Department of Chemistry and Department of Biotechnology, BOKU-University of Natural Resources and Life Sciences, Vienna, Muthgasse 18, A-1190 Vienna, Austria.

Funding

Austrian Science Fund FWF W 1224
6 · The paper itself

Abstract

Targeting two unique antigens with a single bispecific antibody is an attractive approach with potential broad therapeutic applicability. However, the production of heterodimeric bispecific antibodies (bsAbs) presents a challenge, requiring the co-expression and accurate pairing of two distinct heavy and light chain units. Several undesirable by-products can be formed in the production process, including heavy chain homodimers and non-cognate light chain pairings. Although additional downstream purification methods exist, they are often time consuming and restrict practical large-scale production. In this study, we identify and validate novel Fab interface mutations that increase cognate light chain pairing efficiencies within heterodimeric bsAbs. Importantly, the variable domains remain unaltered as interface mutations were restricted to the CH1 and CL domains. We performed several biochemical assays to demonstrate that the novel engineered interfaces do not adversely impact bispecific antibody expression, stability, affinity and biological function. The designs reported here can easily be applied in a generic manner to use existing antibodies as building blocks for bsAbs which will help to accelerate the identification and production of next generation bispecific antibody therapeutics.

Indexed as

AnimalsAntibodies, BispecificCHO CellsCricetulusGene ExpressionHEK293 CellsHumansImmunoglobulin Fab FragmentsImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsModels, MolecularMutationPlasmidsProtein BindingProtein EngineeringProtein Interaction Domains and MotifsAntibodies, BispecificImmunoglobulin Fab FragmentsImmunoglobulin Heavy ChainsImmunoglobulin Light ChainsRecombinant Proteinsbispecific antibodiesFab interface designheterodimeric IgGlight chain pairing problemorthogonal Fab engineering

Identifiers

PMID28981885
PMCPMC5914326

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.