Evidence map›Paper›PMID 35014603›Full record

ArticlemAbs

Beyond bispecificity: Controlled Fab arm exchange for the generation of antibodies with multiple specificities.

Desislava Yanakieva, Lukas Pekar, Andreas Evers, Markus Fleischer, Stephan Keller, Dirk Mueller-Pompalla, Lars Toleikis, Harald Kolmar, Stefan Zielonka, Simon Krah

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In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Article
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  6. Article
  7. Enhancing NK cell-mediated tumor killing of B7-H6Molecular therapy. Oncology · 2025
    Article
  8. Article
  9. Article
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  11. Article
  12. Review
  13. Article
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  19. VInternational journal of molecular sciences · 2022
    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.

Desislava YanakievaInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
Lukas PekarProtein Engineering and Antibody Technologies, Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Darmstadt, Germany.
Andreas EversProtein Engineering and Antibody Technologies, Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Darmstadt, Germany.
Markus FleischerProtein and Cell Sciences, Merck Healthcare KGaA, Darmstadt, Germany.
Stephan KellerProtein and Cell Sciences, Merck Healthcare KGaA, Darmstadt, Germany.
Dirk Mueller-PompallaProtein and Cell Sciences, Merck Healthcare KGaA, Darmstadt, Germany.
Lars ToleikisProtein Engineering and Antibody Technologies, Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Darmstadt, Germany.
Harald KolmarInstitute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Darmstadt, Germany.
Stefan ZielonkaProtein Engineering and Antibody Technologies, Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Darmstadt, Germany.
Simon KrahProtein Engineering and Antibody Technologies, Protein Engineering and Antibody Technologies, Merck Healthcare KGaA, Darmstadt, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Controlled Fab arm exchange (cFAE) has proven to be a generic and versatile technology for the efficient generation of IgG-like bispecific antibodies (DuoBodies or DBs), with several in clinical development and one product, amivantamab, approved by the Food and Drug Administration. In this study, we expand the cFAE-toolbox by incorporating VHH-modules at the C-termini of DB-IgGs, termed DB-VHHs. This approach enables the combinatorial generation of tri- and tetraspecific molecules with flexible valencies in a straightforward fashion. Using cFAE, a variety of multispecific molecules was produced and assessed for manufacturability and physicochemical characteristics. In addition, we were able to generate DB-VHHs that efficiently triggered natural killer cell mediated lysis of tumor cells, demonstrating the utility of this format for potential therapeutic applications.

Indexed as

Antibodies, BispecificImmunoglobulin Fab FragmentsProtein EngineeringAntibody SpecificityHumansamivantamabAntibodies, BispecificImmunoglobulin Fab FragmentscFAEcontrolled Fab arm exchangeduobodyfusion proteinIgG-VHHmultispecificNK cell engagertetraspecifictrispecificVHH

Identifiers

PMID35014603
PMCPMC8757479

What OpenQuestion holds

Textmetadata
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.