Evidence map›Paper›PMID 31879340›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Kappa-on-Heavy (KoH) bodies are a distinct class of fully-human antibody-like therapeutic agents with antigen-binding properties.

Lynn E Macdonald, Karoline A Meagher, Matthew C Franklin, Natasha Levenkova, Johanna Hansen, Ashok T Badithe, Maggie Zhong, Pamela Krueger, Ashique Rafique, Naxin Tu and 20 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 40% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
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

30 authors at 1 institution in 1 country.

Lynn E MacdonaldRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591 lynn.macdonald@regeneron.com.ORCID 0000-0002-2547-4523
Karoline A MeagherRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Matthew C FranklinRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Natasha LevenkovaRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.ORCID 0000-0001-9622-185X
Johanna HansenRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Ashok T BaditheRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Maggie ZhongRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.ORCID 0000-0003-4632-7909
Pamela KruegerRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.ORCID 0000-0002-6166-7189
Ashique RafiqueRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Naxin TuRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
James ShevchukRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Saurabh WadhwaRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
George EhrlichRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Joannie BautistaRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Craig GrantRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Lakeisha EsauRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
William T PoueymirouRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Wojtek AuerbachRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Lori MortonRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Robert BabbRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Gang ChenRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Tammy HuangRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.ORCID 0000-0003-0127-4743
Douglas MacDonaldRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Kenneth GrahamRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Cagan GurerRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Vera A VoroninaRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.ORCID 0000-0002-8934-3530
John R McWhirterRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Chunguang GuoRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
George D YancopoulosRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Andrew J MurphyRegeneron Tech Centers, Regeneron Pharmaceuticals, Inc., Tarrytown, NY 10591.
Regeneron (United States) · US

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

We describe a Kappa-on-Heavy (KoH) mouse that produces a class of highly diverse, fully human, antibody-like agents. This mouse was made by replacing the germline variable sequences of both the Ig heavy-chain (IgH) and Ig kappa (IgK) loci with the human IgK germline variable sequences, producing antibody-like molecules with an antigen binding site made up of 2 kappa variable domains. These molecules, named KoH bodies, structurally mimic naturally existing Bence-Jones light-chain dimers in their variable domains and remain wild-type in their antibody constant domains. Unlike artificially diversified, nonimmunoglobulin alternative scaffolds (e.g., DARPins), KoH bodies consist of a configuration of normal Ig scaffolds that undergo natural diversification in B cells. Monoclonal KoH bodies have properties similar to those of conventional antibodies but exhibit an enhanced ability to bind small molecules such as the endogenous cardiotonic steroid marinobufagenin (MBG) and nicotine. A comparison of crystal structures of MBG bound to a KoH Fab versus a conventional Fab showed that the KoH body has a much deeper binding pocket, allowing MBG to be held 4 Å further down into the combining site between the 2 variable domains.

Indexed as

AnimalsAntibodiesAntigensBase SequenceBinding Sites, AntibodyBufanolidesGenetic EngineeringHumansImmunoglobulin Heavy ChainsImmunoglobulin kappa-ChainsImmunoglobulin Variable RegionMiceModels, MolecularNicotineProtein ConformationAntibodiesAntigensBufanolidesImmunoglobulin Heavy ChainsImmunoglobulin kappa-ChainsImmunoglobulin Variable RegionmarinobufageninNicotinealternative binding scaffoldsimmunoglobulin locitherapeutic antibodies

Identifiers

PMID31879340
PMCPMC6955234
OpenAlexW3021257611

What OpenQuestion holds

Textmetadata
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.