Evidence map›Paper›PMID 30900945›Full record

ArticlemAbs

Immune repertoire mining for rapid affinity optimization of mouse monoclonal antibodies.

Yi-Chun Hsiao, Yonglei Shang, Danielle M DiCara, Angie Yee, Joyce Lai, Si Hyun Kim, Diego Ellerman, Racquel Corpuz, Yongmei Chen, Sharmila Rajan and 4 more

Open access · goldAbstract read
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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

13 citing papers in PubMed, 31 citations in OpenAlex.

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  10. Trace Reconstruction Problems in Computational Biology.IEEE transactions on information theory · 2021
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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.

Yi-Chun Hsiaoa Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Yonglei Shanga Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Danielle M DiCaraa Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Angie Yeea Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Joyce Laia Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Si Hyun Kima Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.ORCID 0000-0002-5468-9427
Diego Ellermanb Department of Structural Biology and Protein Chemistry , Genentech , South San Francisco , CA , USA.ORCID 0000-0002-3056-3600
Racquel Corpuzb Department of Structural Biology and Protein Chemistry , Genentech , South San Francisco , CA , USA.
Yongmei Chena Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Sharmila Rajanc Department of Preclinical and Translational Pharmacokinetics , Genentech , South San Francisco , CA , USA.
Hao Caic Department of Preclinical and Translational Pharmacokinetics , Genentech , South San Francisco , CA , USA.ORCID 0000-0002-4937-085X
Yan Wua Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.
Dhaya Seshasayeea Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.ORCID 0000-0002-8430-3433
Isidro Hötzela Department of Antibody Engineering , Genentech , South San Francisco , CA , USA.ORCID 0000-0001-6910-7840

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Traditional hybridoma and B cell cloning antibody discovery platforms have inherent limits in immune repertoire sampling depth. One consequence is that monoclonal antibody (mAb) leads often lack the necessary affinity for therapeutic applications, thus requiring labor-intensive and time-consuming affinity in vitro engineering optimization steps. Here, we show that high-affinity variants of mouse-derived mAbs can be rapidly obtained by testing of somatic sequence variants obtained by deep sequencing of antibody variable regions in immune repertories from immunized mice, even with a relatively sparse sampling of sequence variants from large sequence datasets. Affinity improvements can be achieved for mAbs with a wide range of affinities. The optimized antibody variants derived from immune repertoire mining have no detectable in vitro off-target binding and have in vivo clearance comparable to the parental mAbs, essential properties in therapeutic antibody leads. As generation of antibody variants in vitro is replaced by mining of variants generated in vivo, the procedure can be applied to rapidly identify affinity-optimized mAb variants.

Indexed as

alpha-SynucleinAnimalsAntibodies, MonoclonalAntibody AffinityB-LymphocytesClone CellsHigh-Throughput Nucleotide SequencingHumansHybridomasImmunizationImmunoglobulin Variable RegionMiceMice, Inbred C57BLParkinson DiseaseSomatic Hypermutation, Immunoglobulinalpha-SynucleinAntibodies, MonoclonalImmunoglobulin Variable Regionaffinity maturationantibodyomeimmunoglobulinNext-generation sequencingNGSsomatic mutation

Identifiers

PMID30900945
PMCPMC6601555
OpenAlexW2941947447

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.