Evidence map›Paper›PMID 28910564›Full record

ArticlemAbs2017

Nonspecificity in a nonimmune human scFv repertoire.

Ryan L Kelly, Jessie Zhao, Doris Le, K Dane Wittrup

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

21 citing papers in PubMed, 28 citations in OpenAlex.

  1. Article
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  15. Toward Drug-Like Multispecific Antibodies by Design.International journal of molecular sciences · 2020
    Review
  16. Article
  17. Review
  18. Nature-inspired design and evolution of anti-amyloid antibodies.The Journal of biological chemistry · 2019
    Article
  19. Article
  20. 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

4 authors at 1 institution in 1 country.

Ryan L Kellya Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge , MA , U.S.A.
Jessie Zhaob Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge , MA , U.S.A.
Doris Leb Department of Chemical Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge , MA , U.S.A.
K Dane Wittrupa Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge , MA , U.S.A.
Massachusetts Institute of Technology · US

Funding

Interdepartmental Biotechnology Training ProgramT32GM008334 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 1989 to 2018
$15.2M
NIGMS NIH HHS T32 GM008334
6 · The paper itself

Abstract

Efforts to develop effective antibody therapeutics are frequently hampered by issues such as aggregation and nonspecificity, often only detected in late stages of the development process. In this study, we used a high throughput cross-reactivity assay to select nonspecific clones from a naïve human repertoire scFv library displayed on the surface of yeast. Most antibody families were de-enriched; however, the rarely expressed VH6 family was highly enriched among nonspecific clones, representing almost 90% of isolated clones. Mutational analysis of this family reveals a dominant role of CDRH2 in driving nonspecific binding. Homology modeling of a panel of VH6 antibodies shows a constrained β-sheet structure in CDRH2 that is not present in other families, potentially contributing to nonspecificity of the family. These findings confirm the common decision to exclude VH6 from synthetic antibody libraries, and support VH6 polyreactivity as a possible important role for the family in early ontogeny and cause for its overabundance in cases of some forms of autoimmunity.

Indexed as

Antibody SpecificityHumansSingle-Chain AntibodiesSingle-Chain Antibodiescomplementarity determining regioncross-interactionmonoclonal antibodynatural repertoireNonspecificitypolyreactivityVH6

Identifiers

PMID28910564
PMCPMC5627588
OpenAlexW2756462780

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.