Evidence map›Paper›PMID 39823326›Full record

ArticleScience advances2025

Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.

Virginia Metrangolo, Michaela Hansen Blomquist, Ananya Dutta, Henrik Gårdsvoll, Oliver Krigslund, Kirstine Sandal Nørregaard, Henrik Jessen Jürgensen, Michael Ploug, Matthew J Flick, Niels Behrendt and 1 more

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
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  4. Review
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  8. Targeted therapy and biomarker-guided applications of ecofriendly silver nanoparticles in precision oncology.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2025
    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

11 authors.

Virginia MetrangoloThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0002-1479-8581
Michaela Hansen BlomquistThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Ananya DuttaDepartment of Medicine, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-8287-8970
Henrik GårdsvollThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0003-0691-3567
Oliver KrigslundThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0002-4032-0426
Kirstine Sandal NørregaardThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0002-1299-0991
Henrik Jessen JürgensenThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0003-4405-2307
Michael PlougThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0003-2215-4265
Matthew J FlickDepartment of Medicine and the UNC Blood Research Center, University of North Carolina, Chapel Hill, NC 27599, USA.ORCID 0000-0002-5034-3162
Niels BehrendtThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.
Lars H EngelholmThe Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark.ORCID 0000-0002-6616-1232

Funding

Reprogramming PDAC Stroma by Targeting Coagulation in the Tumor MicroenvironmentU01CA274304 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Melissa L. Fishel, Matthew J. Flick · 2022 to 2026
$4.6M
Targeting the Plasminogen Activation System to Limit Pancreatic Cancer Progression and Associated ThrombosisU01HL143403 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI FISHEL, MELISSA L., FLICK, MATTHEW J. · 2018 to 2022
$4.2M
NCI NIH HHS U01 CA274304NHLBI NIH HHS U01 HL143403
6 · The paper itself

Abstract

Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692). In vitro, FL1-PNU exhibited potent and specific cytotoxicity against uPAR-expressing PDAC cell lines, stromal and immune cells, and bystander killing of uPAR-negative cells. In vivo, the ADC induced remission or sustained tumor regression and extended survival in xenograft models. In syngeneic orthotopic models, the antitumor effect promoted immunomodulation by enhancing infiltrating immune effectors and decreasing immunosuppressive cells. This study lays grounds for further exploring FL1-PNU as a putative clinical ADC candidate, potentially providing a promising therapeutic avenue for PDAC as a monotherapy or in combinatorial regimens.

Indexed as

Carcinoma, Pancreatic DuctalImmunoconjugatesPancreatic NeoplasmsReceptors, Urokinase Plasminogen ActivatorAnimalsAntibodies, MonoclonalCell Line, TumorCell ProliferationDisease Models, AnimalFemaleHumansMiceXenograft Model Antitumor AssaysAntibodies, MonoclonalImmunoconjugatesReceptors, Urokinase Plasminogen Activator

Identifiers

PMID39823326
PMCPMC11740940

What OpenQuestion holds

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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.