Evidence map›Paper›PMID 31822703›Full record

ArticleScientific reports2019

Intracellular delivery of therapeutic antibodies into specific cells using antibody-peptide fusions.

Julie Gaston, Nicolas Maestrali, Guilhem Lalle, Marie Gagnaire, Alessandro Masiero, Bruno Dumas, Tarik Dabdoubi, Katarina Radošević, Pierre-François Berne

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.7field-weighted citation impact, top 9% 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

29 citing papers in PubMed, 65 citations in OpenAlex.

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  4. Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025
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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

9 authors at 2 institutions in 1 country.

Julie GastonYubsis, 4 rue Pierre Fontaine, 91000, Evry, France.
Nicolas MaestraliSanofi R&D, Biologics Research, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France.
Guilhem LalleDepartment of Immunology, Virology and Inflammation, UMR INSERM 1052, CNRS 5286, Centre Léon Bérard, Labex DEVweCAN, 693743, Lyon, France.
Marie GagnaireSanofi R&D, Biologics Research, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France.ORCID http://orcid.org/0000-0002-4993-3421
Alessandro MasieroSanofi R&D, Biologics Research, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France.
Bruno DumasSanofi R&D, Biologics Research, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France.
Tarik DabdoubiSanofi R&D, Biologics Research, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France.
Katarina RadoševićSanofi R&D, Biologics Research, 13 Quai Jules Guesde, 94400, Vitry-sur-Seine, France. katarina.radosevic@sanofi.com.ORCID http://orcid.org/0000-0002-6769-8402
Pierre-François BerneYubsis, 4 rue Pierre Fontaine, 91000, Evry, France.
Sanofi (France) · FRCentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Because of their favorable properties as macromolecular drugs, antibodies are a very successful therapeutic modality for interfering with disease-relevant targets in the extracellular space or at the cell membrane. However, a large number of diseases involve cytosolic targets and designing antibodies able to efficiently reach intracellular compartments would expand the antibody-tractable conditions. Here, we genetically fused cell penetrating peptides (CPPs) at various positions to an antibody targeting cancer cells, evaluated the developability features of the resulting antibody-peptide fusions and the ability of selected constructs to reach the cytosol. We first determined positions in the IgG structure that were permissive to CPP incorporation without destabilizing the antibody. Fusing CPPs to the C-terminus of the light chain and either before or after the hinge had the least effect on antibody developability features. These constructs were further evaluated for cell penetration efficiency. Two out of five tested CPPs significantly enhanced antibody penetration into the cytosol, in particular when fused before or after the hinge. Finally, we demonstrate that specific antibody binding to the cell surface target is necessary for efficient cell penetration of the CPP-antibody fusions. This study provides a solid basis for further exploration of therapeutic antibodies for intracellular targets.

Indexed as

Drug Delivery SystemsAnimalsAntibodiesCarcinoembryonic AntigenCell Line, TumorCell MembraneCell-Penetrating PeptidesCell SeparationCytoplasmCytosolExtracellular SpaceFlow CytometryGPI-Linked ProteinsGreen Fluorescent ProteinsHEK293 CellsHumansAntibodiesCarcinoembryonic AntigenCEACAM5 protein, humanCell-Penetrating PeptidesGPI-Linked ProteinsGreen Fluorescent ProteinsImmunoglobulin GRecombinant Fusion Proteins

Identifiers

PMID31822703
PMCPMC6904672
OpenAlexW2994631997

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.