Evidence map›Paper›PMID 25774965›Full record

ArticlemAbs2015

Fab-based bispecific antibody formats with robust biophysical properties and biological activity.

Xiufeng Wu, Arlene J Sereno, Flora Huang, Steven M Lewis, Ricky L Lieu, Caroline Weldon, Carina Torres, Cody Fine, Micheal A Batt, Jonathan R Fitchett and 3 more

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
5.7field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Shared PRAME epitopes are T-cell targets in NUT carcinoma.Journal for immunotherapy of cancer · 2026
    Article
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  4. Review
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  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Dopamine DBiomolecules · 2022
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. 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

13 authors at 4 institutions in 2 countries.

Xiufeng Wua Eli Lilly Biotechnology Center ; San Diego , CA , USA.
Arlene J Sereno
Flora Huang
Steven M Lewis
Ricky L Lieu
Caroline Weldon
Carina Torres
Cody Fine
Micheal A Batt
Jonathan R Fitchett
Andrew L Glasebrook
Brian Kuhlman
Stephen J Demarest
University of California, San Diego · USEli Lilly (United States) · USUNC Lineberger Comprehensive Cancer CenterUniversity of North Carolina at Chapel Hill · US

Funding

Designing Affinity and Specificity at Protein InterfacesR01GM073960 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KUHLMAN, BRIAN A · 2005 to 2018
$3.1M
NIGMS NIH HHS R01 GM073960
6 · The paper itself

Abstract

A myriad of innovative bispecific antibody (BsAb) platforms have been reported. Most require significant protein engineering to be viable from a development and manufacturing perspective. Single-chain variable fragments (scFvs) and diabodies that consist only of antibody variable domains have been used as building blocks for making BsAbs for decades. The drawback with Fv-only moieties is that they lack the native-like interactions with CH1/CL domains that make antibody Fab regions stable and soluble. Here, we utilize a redesigned Fab interface to explore 2 novel Fab-based BsAbs platforms. The redesigned Fab interface designs limit heavy and light chain mixing when 2 Fabs are co-expressed simultaneously, thus allowing the use of 2 different Fabs within a BsAb construct without the requirement of one or more scFvs. We describe the stability and activity of a HER2×HER2 IgG-Fab BsAb, and compare its biophysical and activity properties with those of an IgG-scFv that utilizes the variable domains of the same parental antibodies. We also generated an EGFR × CD3 tandem Fab protein with a similar format to a tandem scFv (otherwise known as a bispecific T cell engager or BiTE). We show that the Fab-based BsAbs have superior biophysical properties compared to the scFv-based BsAbs. Additionally, the Fab-based BsAbs do not simply recapitulate the activity of their scFv counterparts, but are shown to possess unique biological activity.

Indexed as

Antibodies, BispecificRecombinant Fusion ProteinsSingle-Chain AntibodiesCell Line, TumorHumansProtein StabilityAntibodies, BispecificRecombinant Fusion ProteinsSingle-Chain Antibodiesbispecific antibodyBiTE, bispecific T cell engagerBsAb, bispecific antibodyCD, circular dichroismDSC, differential scanning calorimetryFab, antigen binding antibody fragmentFab interface designFv, variable domains antibody fragmentHC, antibody heavy chainIgG-FabLC, antibody light chainLCMS, liquid chromatography with in-line mass spectrometrymAb, monoclonal antibodyscFv, single chain FvSEC-LC, size exclusion chromatography with in-line static light scatteringtandem FabT cellTm, temperature at the midpoint of thermal unfolding

Identifiers

PMID25774965
PMCPMC4622572
OpenAlexW1551575829

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.