Evidence map›Paper›PMID 41143950›Full record

ArticleBioconjugate chemistry2025

Development of a Mesothelin-Binding Engineered Scaffold Protein as a Theranostic for Pleural Mesothelioma.

Roberto Silvestri, Margherita Piccardi, Alessia Laurenza, Filomena Rea, Allison R Sirois, Martina Lari, Francesco Bartoli, Giovanni Signore, Lorena Tedeschi, Elisabetta Ferraro and 5 more

Abstract read
In one paragraph

Article in Bioconjugate chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

15 authors.

Roberto SilvestriDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Margherita PiccardiDepartment of Biology, University of Pisa, Pisa 56126, Italy.ORCID 0000-0002-5199-4522
Alessia LaurenzaDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Filomena ReaDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56126, Italy.
Allison R SiroisPicker Engineering Program, Smith College, Northampton, Massachusetts 01063, United States.
Martina LariDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Francesco BartoliDepartment of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa 56126, Italy.
Giovanni SignoreDepartment of Biology, University of Pisa, Pisa 56126, Italy.ORCID 0000-0002-0067-2240
Lorena TedeschiInstitute of Clinical Physiology, CNR, Pisa 56124, Italy.ORCID 0000-0002-8898-0888
Elisabetta FerraroDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Paola Anna ErbaSchool of Medicine and Surgery, University of Milan Bicocca, Milan 20126, Italy.
Roberto GiovannoniDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Stefano LandiDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Federica GemignaniDepartment of Biology, University of Pisa, Pisa 56126, Italy.
Sarah J MoorePicker Engineering Program, Smith College, Northampton, Massachusetts 01063, United States.ORCID 0000-0002-2633-4020

Funding

Engineering therapeutic and diagnostic proteins for tumor biomarker mesothelinR15CA198927 · NCI · SMITH COLLEGE · PI MOORE, SARAH J. · 2015 to 2015
$399k
NCI NIH HHS R15 CA198927
6 · The paper itself

Abstract

Mesothelin (MSLN) is a tumor biomarker expressed at high levels on the surface of numerous cancers with extremely limited expression in healthy tissues. MSLN-targeting agents developed for diagnosis and therapy could have a significant impact on the management of MSLN-expressing cancers. Pleural mesothelioma (PM) is a deadly cancer that arises from mesothelial cells lining the pleura and is predominantly linked to asbestos exposure. There are currently no effective treatments, and diagnosis occurs in late stages of disease due to the lack of clinical symptoms in the early stages. Recent efforts to diagnose and treat PM have focused on identifying and targeting relevant biomarkers, including MSLN. We engineered proteins based on the nonantibody fibronectin type III (Fn3) protein scaffold that bind MSLN with high affinity and specificity, using yeast-surface display and directed evolution. Previous work with Fn3 scaffold proteins has demonstrated tissue distribution desirable for applications in molecular imaging and targeted radiotherapy, which may overcome limitations encountered thus far with antibody-based approaches to treat PM. The MSLN-targeting Fn3 was further developed for bioconjugation with the 1,4,7,10-tetraazacyclododecane,1-(glutaric acid)-4,7,10-triacetic acid (DOTAGA) radiometal chelator. MSLN-binding Fn3 specifically binds to the MSLN-expressing PM lines, colocalizes with MSLN, and internalizes upon binding. Fn3-DOTAGA was further coupled with cold metal gallium-69, and the resulting conjugate maintained binding with high affinity to MSLN-expressing PM cells. MSLN-binding Fn3-DOTAGA-

Indexed as

FibronectinsGPI-Linked ProteinsMesotheliomaPleural NeoplasmsProtein EngineeringTheranostic NanomedicineCell Line, TumorHumansMesothelinProtein BindingFibronectinsGPI-Linked ProteinsMesothelinMSLN protein, human

Identifiers

PMID41143950
PMCPMC12635973

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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.