Evidence map›Paper›PMID 30713798›Full record

ArticleOncoimmunology

Blockade of TGF-β signaling with novel synthetic antibodies limits immune exclusion and improves chemotherapy response in metastatic ovarian cancer models.

Daniel Newsted, Sunandan Banerjee, Kathleen Watt, Sarah Nersesian, Peter Truesdell, Levi L Blazer, Lia Cardarelli, Jarrett J Adams, Sachdev S Sidhu, Andrew W Craig

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

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 12% 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

37 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 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

10 authors at 2 institutions in 1 country.

Daniel NewstedDepartment of Biomedical and Molecular Sciences, Queen's University; Cancer Biology & Genetics division, Queen's Cancer Research Institute, Kingston, ON, Canada.
Sunandan BanerjeeThe Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Kathleen WattDepartment of Biomedical and Molecular Sciences, Queen's University; Cancer Biology & Genetics division, Queen's Cancer Research Institute, Kingston, ON, Canada.
Sarah NersesianDepartment of Biomedical and Molecular Sciences, Queen's University; Cancer Biology & Genetics division, Queen's Cancer Research Institute, Kingston, ON, Canada.
Peter TruesdellDepartment of Biomedical and Molecular Sciences, Queen's University; Cancer Biology & Genetics division, Queen's Cancer Research Institute, Kingston, ON, Canada.
Levi L BlazerThe Donnelly Centre, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-9594-4642
Lia CardarelliThe Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Jarrett J AdamsThe Donnelly Centre, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-0182-922X
Sachdev S SidhuThe Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Andrew W CraigDepartment of Biomedical and Molecular Sciences, Queen's University; Cancer Biology & Genetics division, Queen's Cancer Research Institute, Kingston, ON, Canada.ORCID 0000-0002-2039-2393
Queen's University · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epithelial ovarian cancer (EOC) is a leading cause of cancer-related death in women. EOC is often diagnosed at late stages, with peritoneal metastases and ascites production. Current surgery and platinum-based chemotherapy regimes fail to prevent recurrence in most patients. High levels of Transforming growth factor-β (TGF-β) within ascites has been linked to poor prognosis. TGF-β signaling promotes epithelial-mesenchymal transition (EMT) in EOC tumor cells, and immune suppression within the tumor microenvironment, with both contributing to chemotherapy resistance and metastasis. The goal of this study was to develop specific synthetic inhibitory antibodies to the Type II TGF-β receptor (TGFBR2), and test these antibodies in EOC cell and tumor models. Following screening of a phage-displayed synthetic antigen-binding fragment (Fab) library with the extracellular domain of TGFBR2, we identified a lead inhibitory Fab that suppressed TGF-β signaling in mouse and human EOC cell lines. Affinity maturation of the lead inhibitory Fab resulted in several derivative Fabs with increased affinity for TGFBR2 and efficacy as suppressors of TGF-β signaling, EMT and EOC cell invasion. In EOC xenograft and syngeneic tumor models, blockade of TGFBR2 with our lead antibodies led to improved chemotherapy response. This correlated with reversal of EMT and immune exclusion in these tumor models with TGFBR2 blockade. Together, these results describe new inhibitors of the TGF-β pathway that improve antitumor immunity, and response to chemotherapy in preclinical EOC models.

Indexed as

combination therapiesEMTimmune exclusionOvarian cancersynthetic antibodiesTGF-β

Identifiers

PMID30713798
PMCPMC6343786
OpenAlexW2901910720

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.