Evidence map›Paper›PMID 30287940›Full record

ArticleScientific reports2018

Humanization of Antibodies using a Statistical Inference Approach.

Alejandro Clavero-Álvarez, Tomas Di Mambro, Sergio Perez-Gaviro, Mauro Magnani, Pierpaolo Bruscolini

Abstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

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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

24 citing papers in PubMed.

  1. Article
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  8. Computational and structural biotechnology journal · 2024
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  20. AbRSA: A robust tool for antibody numbering.Protein science : a publication of the Protein Society · 2019
    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

5 authors.

Alejandro Clavero-ÁlvarezDepartamento de Física Teórica, Universidad de Zaragoza, Zaragoza, 50009, Spain.
Tomas Di MambroDepartment of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
Sergio Perez-GaviroDepartamento de Física Teórica, Universidad de Zaragoza, Zaragoza, 50009, Spain.
Mauro MagnaniDepartment of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy.
Pierpaolo BruscoliniDepartamento de Física Teórica, Universidad de Zaragoza, Zaragoza, 50009, Spain. pier@unizar.es.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibody humanization is a key step in the preclinical phase of the development of therapeutic antibodies, originally developed and tested in non-human models (most typically, in mouse). The standard technique of Complementarity-Determining Regions (CDR) grafting into human Framework Regions of germline sequences has some important drawbacks, in that the resulting sequences often need further back-mutations to ensure functionality and/or stability. Here we propose a new method to characterize the statistical distribution of the sequences of the variable regions of human antibodies, that takes into account phenotypical correlations between pairs of residues, both within and between chains. We define a "humanness score" of a sequence, comparing its performance in distinguishing human from murine sequences, with that of some alternative scores in the literature. We also compare the score with the experimental immunogenicity of clinically used antibodies. Finally, we use the humanness score as an optimization function and perform a search in the sequence space, starting from different murine sequences and keeping the CDR regions unchanged. Our results show that our humanness score outperforms other methods in sequence classification, and the optimization protocol is able to generate humanized sequences that are recognized as human by standard homology modelling tools.

Indexed as

AnimalsAntibodies, MonoclonalBiostatisticsComplementarity Determining RegionsComputational BiologyHumansImmunoglobulin Variable RegionImmunologic FactorsMiceRecombinant ProteinsAntibodies, MonoclonalComplementarity Determining RegionsImmunoglobulin Variable RegionImmunologic FactorsRecombinant Proteins

Identifiers

PMID30287940
PMCPMC6172228

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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.