Evidence map›Paper›PMID 29376776›Full record

ArticlemAbs2018

A natively paired antibody library yields drug leads with higher sensitivity and specificity than a randomly paired antibody library.

Adam S Adler, Daniel Bedinger, Matthew S Adams, Michael A Asensio, Robert C Edgar, Renee Leong, Jackson Leong, Rena A Mizrahi, Matthew J Spindler, Srinivasa Rao Bandi and 4 more

Open access · goldAbstract read
In one paragraph

Article in mAbs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

31 citing papers in PubMed, 40 citations in OpenAlex.

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  9. Fluorescence-activated droplet sequencing (FAD-seq) directly provides sequences of screening hits in antibody discovery.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  20. How repertoire data are changing antibody science.The Journal of biological chemistry · 2020
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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

14 authors at 3 institutions in 1 country.

Adam S Adlera GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Daniel Bedingerb Carterra Inc. , 825 N 300 W, Suite C309, Salt Lake City , UT USA.
Matthew S Adamsa GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Michael A Asensioa GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Robert C Edgara GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Renee Leonga GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Jackson Leonga GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Rena A Mizrahia GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Matthew J Spindlera GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
Srinivasa Rao Bandic Bristol-Myers Squibb , 700 Bay Road, Redwood City , CA USA.
Haichun Huangc Bristol-Myers Squibb , 700 Bay Road, Redwood City , CA USA.
Pallavi Tawdec Bristol-Myers Squibb , 700 Bay Road, Redwood City , CA USA.ORCID 0000-0003-1863-9569
Peter Bramsc Bristol-Myers Squibb , 700 Bay Road, Redwood City , CA USA.
David S Johnsona GigaGen Inc., One Tower Place , Suite 750, South San Francisco , CA USA.
GigaGen (United States) · USBristol-Myers Squibb (United States) · USCarterra (United States) · US

Funding

Next-Generation Antibody Discovery and Development TechnologyR44CA187852 · NCI · GIGAGEN, INC. · PI JOHNSON, DAVID SCOTT · 2016 to 2018
$1.6M
NCI NIH HHS R44 CA187852
6 · The paper itself

Abstract

Deep sequencing and single-chain variable fragment (scFv) yeast display methods are becoming more popular for discovery of therapeutic antibody candidates in mouse B cell repertoires. In this study, we compare a deep sequencing and scFv display method that retains native heavy and light chain pairing with a related method that randomly pairs heavy and light chain. We performed the studies in a humanized mouse, using interleukin 21 receptor (IL-21R) as a test immunogen. We identified 44 high-affinity binder scFv with the native pairing method and 100 high-affinity binder scFv with the random pairing method. 30% of the natively paired scFv binders were also discovered with the randomly paired method, and 13% of the randomly paired binders were also discovered with the natively paired method. Additionally, 33% of the scFv binders discovered only in the randomly paired library were initially present in the natively paired pre-sort library. Thus, a significant proportion of "randomly paired" scFv were actually natively paired. We synthesized and produced 46 of the candidates as full-length antibodies and subjected them to a panel of binding assays to characterize their therapeutic potential. 87% of the antibodies were verified as binding IL-21R by at least one assay. We found that antibodies with native light chains were more likely to bind IL-21R than antibodies with non-native light chains, suggesting a higher false positive rate for antibodies from the randomly paired library. Additionally, the randomly paired method failed to identify nearly half of the true natively paired binders, suggesting a higher false negative rate. We conclude that natively paired libraries have critical advantages in sensitivity and specificity for antibody discovery programs.

Indexed as

Gene LibraryImmunoglobulin Light ChainsInterleukin-21 Receptor alpha SubunitSingle-Chain AntibodiesAnimalsB-LymphocytesHumansMiceIL21R protein, humanImmunoglobulin Light ChainsInterleukin-21 Receptor alpha SubunitSingle-Chain Antibodiesdeep sequencinghumanized mouse antibody repertoiresIL-21Ryeast display

Identifiers

PMID29376776
PMCPMC5916548
OpenAlexW2790933097

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.