Evidence map›Paper›PMID 32522868›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Engineering a potent receptor superagonist or antagonist from a novel IL-6 family cytokine ligand.

Jun W Kim, Cesar P Marquez, R Andres Parra Sperberg, Jiaxiang Wu, Won G Bae, Po-Ssu Huang, E Alejandro Sweet-Cordero, Jennifer R Cochran

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.6field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. CRLF1 and CLCF1 in Development, Health and Disease.International journal of molecular sciences · 2022
    Review
  13. Review
  14. Review
  15. Linking molecular evolution to molecular grafting.The Journal of biological chemistry
    Review
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

8 authors at 4 institutions in 3 countries.

Jun W KimDepartment of Bioengineering, Stanford University, Stanford, CA 94305.ORCID 0000-0001-6325-6204
Cesar P MarquezDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, CA 94158.
R Andres Parra SperbergDepartment of Bioengineering, Stanford University, Stanford, CA 94305.
Jiaxiang WuDepartment of Bioengineering, Stanford University, Stanford, CA 94305.ORCID 0000-0001-9132-5625
Won G BaeDepartment of Electrical Engineering, Soongsil University, 156-743 Seoul, Korea.
Po-Ssu HuangDepartment of Bioengineering, Stanford University, Stanford, CA 94305.ORCID 0000-0002-7948-2895
E Alejandro Sweet-CorderoDivision of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, CA 94158; alejandro.sweet-cordero@ucsf.edu jennifer.cochran@stanford.edu.
Jennifer R CochranDepartment of Bioengineering, Stanford University, Stanford, CA 94305; alejandro.sweet-cordero@ucsf.edu jennifer.cochran@stanford.edu.ORCID 0000-0002-6532-9873
Stanford University · USUniversity of California, San Francisco · USSoongsil University · KRTencent (China) · CN

Funding

Development of novel protein-based therapeutics for lung cancerR01CA225103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASSIK, MICHAEL C, COCHRAN, JENNIFER R · 2018 to 2022
$2.8M
Elucidating the Role of the CLCF1-CNTFR Signaling Axis for Lung Cancer TreatmentF31CA236324 · NCI · STANFORD UNIVERSITY · PI MARQUEZ, CESAR · 2018 to 2021
$174k
Howard Hughes Medical InstituteNCI NIH HHS F31 CA236324NCI NIH HHS R01 CA225103
6 · The paper itself

Abstract

Interleukin-6 (IL-6) family cytokines signal through multimeric receptor complexes, providing unique opportunities to create novel ligand-based therapeutics. The cardiotrophin-like cytokine factor 1 (CLCF1) ligand has been shown to play a role in cancer, osteoporosis, and atherosclerosis. Once bound to ciliary neurotrophic factor receptor (CNTFR), CLCF1 mediates interactions to coreceptors glycoprotein 130 (gp130) and leukemia inhibitory factor receptor (LIFR). By increasing CNTFR-mediated binding to these coreceptors we generated a receptor superagonist which surpassed the potency of natural CNTFR ligands in neuronal signaling. Through additional mutations, we generated a receptor antagonist with increased binding to CNTFR but lack of binding to the coreceptors that inhibited tumor progression in murine xenograft models of nonsmall cell lung cancer. These studies further validate the CLCF1-CNTFR signaling axis as a therapeutic target and highlight an approach of engineering cytokine activity through a small number of mutations.

Indexed as

AnimalsBinding SitesCell Line, TumorCells, CulturedCiliary Neurotrophic Factor Receptor alpha SubunitCytokine Receptor gp130CytokinesHumansLeukemia Inhibitory Factor Receptor alpha SubunitLigandsNeuronsProtein BindingProtein EngineeringRatsSignal TransductionCiliary Neurotrophic Factor Receptor alpha SubunitCLCF1 protein, humanCNTFR protein, humanCytokine Receptor gp130CytokinesLeukemia Inhibitory Factor Receptor alpha SubunitLIFR protein, humanLigandsligand–receptor interactionprotein engineeringyeast surface display

Identifiers

PMID32522868
PMCPMC7322068
OpenAlexW3033287737

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.