Evidence map›Paper›PMID 37408314›Full record

ArticlemAbs

Improved antibody pharmacokinetics by disruption of contiguous positive surface potential and charge reduction using alternate human framework.

Romain Ollier, Aline Fuchs, Florence Gauye, Katarzyna Piorkowska, Sébastien Menant, Monisha Ratnam, Paolo Montanari, Florence Guilhot, Didier Phillipe, Mickael Audrain and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

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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

16 authors at 1 institution in 1 country.

Romain OllierResearch, AC Immune SA, Lausanne, Switzerland.
Aline FuchsResearch, AC Immune SA, Lausanne, Switzerland.
Florence GauyeResearch, AC Immune SA, Lausanne, Switzerland.
Katarzyna PiorkowskaResearch, AC Immune SA, Lausanne, Switzerland.
Sébastien MenantResearch, AC Immune SA, Lausanne, Switzerland.
Monisha RatnamResearch, AC Immune SA, Lausanne, Switzerland.
Paolo MontanariResearch, AC Immune SA, Lausanne, Switzerland.
Florence GuilhotResearch, AC Immune SA, Lausanne, Switzerland.
Didier PhillipeResearch, AC Immune SA, Lausanne, Switzerland.
Mickael AudrainResearch, AC Immune SA, Lausanne, Switzerland.
Anne-Laure EgesipeResearch, AC Immune SA, Lausanne, Switzerland.
Damien NévoltrisResearch, AC Immune SA, Lausanne, Switzerland.
Tamara SeredeninaResearch, AC Immune SA, Lausanne, Switzerland.
Andrea PfeiferResearch, AC Immune SA, Lausanne, Switzerland.
Marie Kosco-VilboisResearch, AC Immune SA, Lausanne, Switzerland.
Tariq AfrozResearch, AC Immune SA, Lausanne, Switzerland.
AC Immune (Switzerland) · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Optimal pharmacokinetic (PK) properties of therapeutic monoclonal antibodies (mAbs) are essential to achieve the desired pharmacological benefits in patients. To accomplish this, we followed an approach comprising structure-based mAb charge engineering in conjunction with the use of relevant preclinical models to screen and select humanized candidates with PK suitable for clinical development. Murine mAb targeting TDP-43, ACI-5891, was humanized on a framework (VH1-3/VK2-30) selected based on the highest sequence homology. Since the initial humanized mAb (ACI-5891.1) presented a fast clearance in non-human primates (NHPs), reiteration of humanization on a less basic human framework (VH1-69-2/VK2-28) while retaining high sequence homology was performed. The resulting humanized variant, ACI-5891.9, presented a six-fold reduction in clearance in NHPs resulting in a significant increase in half-life. The observed reduced clearance of ACI-5891.9 was attributed not only to the overall reduction in isoelectric point (pI) by 2 units, but importantly to a more even surface potential. These data confirm the importance and contribution of surface charges to mAb disposition

Indexed as

Antibodies, MonoclonalReceptors, FcAnimalsHistocompatibility Antigens Class IHumansIsoelectric PointMetabolic Clearance RateMiceMice, TransgenicAntibodies, MonoclonalHistocompatibility Antigens Class IReceptors, Fcantibody charge engineeringantibody developabilityantibody dispositionAntibody humanizationantibody pharmacokineticsFcRn transgenic micepharmacokinetic prediction

Identifiers

PMID37408314
PMCPMC10324452
OpenAlexW4383302078

What OpenQuestion holds

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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.