Evidence map›Paper›PMID 34763607›Full record

ArticlemAbs

Impact of IgG subclass on molecular properties of monoclonal antibodies.

Yu Tang, Paul Cain, Victor Anguiano, James J Shih, Qing Chai, Yiqing Feng

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 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.

  1. Pooled it
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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

6 authors at 2 institutions in 1 country.

Yu TangPharmaceutical Development, Syndax Pharmaceuticals, Waltham, Massachusetts, USA.
Paul CainBiotechnology Discovery Research, Lilly Research Laboratories, Lilly Technology Center North, Indianapolis, Indiana, USA.
Victor AnguianoBioproduct Research & Development, Lilly Research Laboratories, Lilly Technology Center North, Indianapolis, Indiana, USA.
James J ShihBiotechnology Discovery Research, Lilly Research Laboratories, Lilly Biotechnology Center, San Diego, California, USA.ORCID 0000-0002-9906-9723
Qing ChaiBiotechnology Discovery Research, Lilly Research Laboratories, Lilly Biotechnology Center, San Diego, California, USA.ORCID 0000-0002-6273-905X
Yiqing FengBiotechnology Discovery Research, Lilly Research Laboratories, Lilly Technology Center North, Indianapolis, Indiana, USA.ORCID 0000-0002-6090-3370
Eli Lilly (United States) · USSynta Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immunoglobulin G-based monoclonal antibodies (mAbs) have become a dominant class of biotherapeutics in recent decades. Approved antibodies are mainly of the subclasses IgG1, IgG2, and IgG4, as well as their derivatives. Over the decades, the selection of IgG subclass has frequently been based on the needs of Fc gamma receptor engagement and effector functions for the desired mechanism of action, while the effect on drug product developability has been less thoroughly characterized. One of the major reasons is the lack of systematic understanding of the impact of IgG subclass on the molecular properties. Several efforts have been made recently to compare molecular property differences among these IgG subclasses, but the conclusions from these studies are sometimes obscured by the interference from variable regions. To further establish mechanistic understandings, we conducted a systematic study by grafting three independent variable regions onto human IgG1, an IgG1 variant, IgG2, and an IgG4 variant constant domains and evaluating the impact of subclass and variable regions on their molecular properties. Structural and computational analysis revealed specific molecular features that potentially account for the differential behavior of the IgG subclasses observed experimentally. Our data indicate that IgG subclass plays a significant role on molecular properties, either through direct effects or via the interplay with the variable region, the IgG1 mAbs tend to have higher solubility than either IgG2 or IgG4 mAbs in a common pH 6 buffer matrix, and solution behavior relies heavily on the charge status of the antibody at the desirable pH.

Indexed as

Antibodies, MonoclonalAntineoplastic Agents, ImmunologicalHumansImmunoglobulin GReceptors, IgGAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalImmunoglobulin GReceptors, IgGhomology modelinghydrophobicityIgG subclassisoelectric pointMonoclonal antibodiessolubilitythermal unfoldingturbidityviscosity

Identifiers

PMID34763607
PMCPMC8726687
OpenAlexW3212082453

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.