Evidence map›Paper›PMID 22699308›Full record

ArticlemAbs

Production, characterization, and pharmacokinetic properties of antibodies with N-linked mannose-5 glycans.

Marcella Yu, Darren Brown, Chae Reed, Shan Chung, Jeff Lutman, Eric Stefanich, Anne Wong, Jean-Philippe Stephan, Robert Bayer

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

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 3% 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

101 citing papers in PubMed, 1 synthesis or guideline pooled it, 206 citations in OpenAlex.

  1. Biosimilarity and Interchangeability: Principles and Evidence: A Systematic Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2018
    Pooled it
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41 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 2 countries.

Marcella YuOceanside Pharma Technical Development, Genentech, Inc., Oceanside, CA USA.
Darren Brown
Chae Reed
Shan Chung
Jeff Lutman
Eric Stefanich
Anne Wong
Jean-Philippe Stephan
Robert Bayer
GenentechUniversity of California, San Diego · USFramingham State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The effector functions of therapeutic antibodies are strongly affected by the specific glycans added to the Fc domain during post-translational processing. Antibodies bearing high levels of N-linked mannose-5 glycan (Man5) have been reported to exhibit enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) compared with antibodies with fucosylated complex or hybrid glycans. To better understand the relationship between antibodies with high levels of Man5 and their biological activity in vivo, we developed an approach to generate substantially homogeneous antibodies bearing the Man5 glycoform. A mannosidase inhibitor, kifunensine, was first incorporated in the cell culture process to generate antibodies with a distribution of high mannose glycoforms. Antibodies were then purified and treated with a mannosidase for trimming to Man5 in vitro. This 2-step approach can consistently generate antibodies with > 99% Man5 glycan. Antibodies bearing varying levels of Man5 were studied to compare ADCC and Fcγ receptor binding, and they showed enhanced ADCC activity and increased binding affinity to the FcγRIIIA. In addition, the clearance rate of antibodies bearing Man8/9 and Man5 glycans was determined in a pharmacokinetics study in mice. When compared with historical data, the antibodies bearing the high mannose glycoform exhibited faster clearance rate compared with antibodies bearing the fucosylated complex glycoform, while the pharmacokinetic properties of antibodies with Man8/9 and Man5 glycoforms appeared similar. In addition, we identified the presence of a mannosidase in mouse serum that converted most Man8/9 to Man6 after 24 h.

Indexed as

AlkaloidsAnimalsAntibodies, MonoclonalAntibody-Dependent Cell CytotoxicityArea Under CurveBinding, CompetitiveCell Line, TumorCells, CulturedCell SurvivalCHO CellsCricetinaeCricetulusEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin Fc FragmentsAlkaloidsAntibodies, MonoclonalImmunoglobulin Fc FragmentskifunensineMannoseMannosidasesPolysaccharidesReceptors, IgG

Identifiers

PMID22699308
PMCPMC3499342
OpenAlexW2057390178

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.