Evidence map›Paper›PMID 29995563›Full record

ArticlemAbs2018

Massive parallel screening of phage libraries for the generation of repertoires of human immunomodulatory monoclonal antibodies.

Emanuele Sasso, Chiara D'Avino, Margherita Passariello, Anna Morena D'Alise, Daniela Siciliano, Maria Luisa Esposito, Guendalina Froechlich, Riccardo Cortese, Elisa Scarselli, Nicola Zambrano and 2 more

Abstract read
In one paragraph

Article in mAbs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing 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

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

37 citing papers in PubMed.

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  20. Generation of a Retargeted OncolyticInternational journal of molecular sciences · 2021
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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

12 authors.

Emanuele Sassoa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.ORCID 0000-0002-6454-2824
Chiara D'Avinoa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.
Margherita Passarielloa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.
Anna Morena D'Alisec Nouscom srl , Rome , Italy.
Daniela Sicilianoa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.
Maria Luisa Espositod ReiThera srl , Rome Italy.
Guendalina Froechlicha Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.
Riccardo Cortesee Keires AG , Basel , Switzerland.
Elisa Scarsellic Nouscom srl , Rome , Italy.
Nicola Zambranoa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.
Alfredo Nicosiaa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.ORCID 0000-0002-4731-5822
Claudia De Lorenzoa Department of Molecular Medicine and Medical Biotechnology , University of Naples "Federico II" , Napoli ( NA ), Italy.ORCID 0000-0002-6195-5631

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune checkpoints are emerging as novel targets for cancer therapy, and antibodies against them have shown remarkable clinical efficacy with potential for combination treatments to achieve high therapeutic index. This work aims at providing a novel approach for the generation of several novel human immunomodulatory antibodies capable of binding their targets in their native conformation and useful for therapeutic applications. We performed a massive parallel screening of phage libraries by using for the first time activated human lymphocytes to generate large collections of single-chain variable fragments (scFvs) against 10 different immune checkpoints: LAG-3, PD-L1, PD-1, TIM3, BTLA, TIGIT, OX40, 4-1BB, CD27 and ICOS. By next-generation sequencing and bioinformatics analysis we ranked individual scFvs in each collection and identified those with the highest level of enrichment. As a proof of concept of the quality/potency of the binders identified by this approach, human IgGs from three of these collections (i.e., PD-1, PD-L1 and LAG-3) were generated and shown to have comparable or better binding affinity and biological activity than the clinically validated anti-PD-1 mAb nivolumab. The repertoires generated in this work represent a convenient source of agonistic or antagonistic antibodies against the 'Checkpoint Immunome' for preclinical screening and clinical implementation of optimized treatments.

Indexed as

Antibodies, MonoclonalAntineoplastic Agents, ImmunologicalCell Surface Display TechniquesComputational BiologyCostimulatory and Inhibitory T-Cell ReceptorsHigh-Throughput Nucleotide SequencingHumansImmunologic FactorsImmunotherapyMass ScreeningNeoplasmsSingle-Chain AntibodiesAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCostimulatory and Inhibitory T-Cell ReceptorsImmunologic FactorsSingle-Chain Antibodiescancer immunotherapyhigh-throughput sequencingImmune checkpointsimmunomodulatory mAbsscFv

Identifiers

PMID29995563
PMCPMC6204801

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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.