Evidence map›Paper›PMID 30692603›Full record

ArticleScientific reports2019

Directed evolution of super-secreted variants from phage-displayed human Interleukin-2.

Gertrudis Rojas, Tania Carmenate, Julio Felipe Santo-Tomás, Pedro A Valiente, Marlies Becker, Annia Pérez-Riverón, Yaima Tundidor, Yaquelín Ortiz, Jorge Fernandez de Cossio-Diaz, Luis Graça and 2 more

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 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.0field-weighted citation impact, top 23% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

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  9. Improving the secretion of designed protein assemblies through negative design of cryptic transmembrane domains.Proceedings of the National Academy of Sciences of the United States of America · 2023
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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 at 4 institutions in 3 countries.

Gertrudis RojasCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba. grojas@cim.sld.cu.
Tania CarmenateCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Julio Felipe Santo-TomásCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Pedro A ValienteBiology Faculty, La Habana University, 25 e/ I y J, Vedado, Plaza, CP 10400, La Habana, Cuba.ORCID 0000-0002-4776-6017
Marlies BeckerTechnische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics, Department of Biotechnology, Spielmannstraße 7, 38106, Braunschweig, Germany.
Annia Pérez-RiverónCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Yaima TundidorCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Yaquelín OrtizCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Jorge Fernandez de Cossio-DiazCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Luis GraçaInstituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
Stefan DübelTechnische Universität Braunschweig, Institute of Biochemistry, Biotechnology and Bioinformatics, Department of Biotechnology, Spielmannstraße 7, 38106, Braunschweig, Germany.
Kalet LeónCenter of Molecular Immunology, calle 216 esq 15, apartado 16040, Atabey, Playa, CP 11300, La Habana, Cuba.
Center of Molecular Immunology (Cuba) · CUTechnische Universität Braunschweig · DEUniversity of Havana · CUUniversity of Lisbon · PT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Selection from a phage display library derived from human Interleukin-2 (IL-2) yielded mutated variants with greatly enhanced display levels of the functional cytokine on filamentous phages. Introduction of a single amino acid replacement selected that way (K35E) increased the secretion levels of IL-2-containing fusion proteins from human transfected host cells up to 20-fold. Super-secreted (K35E) IL-2/Fc is biologically active in vitro and in vivo, has anti-tumor activity and exhibits a remarkable reduction in its aggregation propensity- the major manufacturability issue limiting IL-2 usefulness up to now. Improvement of secretion was also shown for a panel of IL-2-engineered variants with altered receptor binding properties, including a selective agonist and a super agonist that kept their unique properties. Our findings will improve developability of the growing family of IL-2-derived immunotherapeutic agents and could have a broader impact on the engineering of structurally related four-alpha-helix bundle cytokines.

Indexed as

Amino Acid SubstitutionAnimalsAntineoplastic AgentsCell Line, TumorCell ProliferationCell Surface Display TechniquesCell SurvivalEvolution, MolecularHumansInterleukin-2MiceMice, Inbred C57BLProtein EngineeringReceptors, FcRecombinant Fusion ProteinsAntineoplastic AgentsIL2 protein, humanInterleukin-2Receptors, FcRecombinant Fusion Proteins

Identifiers

PMID30692603
PMCPMC6349883
OpenAlexW2914639442

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.