Evidence mapPaperPMID 41449467Full record

ArticleJournal of experimental & clinical cancer research : CR2025

Revealing erythropoietin variant EV-3 as novel driving force and immunotherapeutic target in human glioblastoma.

Stefania Elena Navone, Giovanni Marfia, Laura Guarnaccia, Massimiliano Rizzaro, Giorgio Fiore, Rolando Campanella, Chiara Gaudino, Daniele Santini, Giovanni Andrea Alotta, Monica Rosa Miozzo and 3 more

Abstract read
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 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

13 authors.

Stefania Elena Navone *Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Center for Aerospace Medicine and Advanced Therapies - CeMATA - Laboratory of Experimental Neurosurgery and Cell Therapy, Unit of Neurosurgery, Milan, Italy.
Giovanni Marfia *Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Center for Aerospace Medicine and Advanced Therapies - CeMATA - Laboratory of Experimental Neurosurgery and Cell Therapy, Unit of Neurosurgery, Milan, Italy.
Laura GuarnacciaFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Center for Aerospace Medicine and Advanced Therapies - CeMATA - Laboratory of Experimental Neurosurgery and Cell Therapy, Unit of Neurosurgery, Milan, Italy.
Massimiliano RizzaroFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Center for Aerospace Medicine and Advanced Therapies - CeMATA - Laboratory of Experimental Neurosurgery and Cell Therapy, Unit of Neurosurgery, Milan, Italy.
Giorgio FioreFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Center for Aerospace Medicine and Advanced Therapies - CeMATA - Laboratory of Experimental Neurosurgery and Cell Therapy, Unit of Neurosurgery, Milan, Italy.
Rolando CampanellaAndremacon Srl, Milan, Italy.
Chiara GaudinoAzienda Ospedaliero Universitaria Policlinico Umberto I, Department of Neuroradiology, Rome, Italy.
Daniele SantiniSapienza University of Rome, Department of Medico-Surgical Sciences and Biotechnologies, Rome, Italy.
Giovanni Andrea AlottaAndremacon Srl, Milan, Italy.
Monica Rosa MiozzoUniversity of Milan, Medical Genetics Unit, Department of Health Sciences, ASST Santi Paolo e Carlo, Milan, Italy.
Emanuela BarillaAndremacon Srl, Milan, Italy.
Marco LocatelliFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Center for Aerospace Medicine and Advanced Therapies - CeMATA - Laboratory of Experimental Neurosurgery and Cell Therapy, Unit of Neurosurgery, Milan, Italy.
Laura RiboniAndremacon Srl, Milan, Italy. l.riboni@andremacon.com.ORCID http://orcid.org/0000-0002-4149-8226

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlioblastoma is the most aggressive primary brain tumor, and, despite intensive studies, remains one of the most fatal malignancy in adult humans. Among multiple onco-promoters produced by glioblastoma cells, erythropoietin was found. However, the presence/function of Epo alternatively spliced variants in cancer remains unexplored. Here, we investigated the expression and role of Epo-variants in glioblastoma, and the therapeutic potential of their targeting through a novel monoclonal antibody (mAb).

methodsTranscripts and protein levels of Epo-variants in a cohort of human brain tumors were evaluated by RT-PCR, ELISA, and immunohistochemistry. Monoclonal antibodies targeting Epo-Vs were prepared and functionally selected by assaying proliferation, migration, stemness, and angiogenesis in glioblastoma patient-derived cells. Antibody affinity for Epo/Epo-variant was determined by SPR. In vivo toxicity and therapeutic efficacy of the lead antibody were evaluated in GBM mouse models.

resultsWe found a significant overexpression of Epo-variant transcripts in tissues and cells from GBM patients. After functional selection of newly-produced antibodies, we identified AND-C4 as the lead one for its potent anti-tumoral properties, absence of anti-erythropoietic effects and of toxicity on human brain cells. AND-C4 exhibited high affinity for the Epo-variant EV-3. We demonstrated that EV-3 was efficiently produced and secreted by glioblastoma cells, particularly by stem cells. EV-3 exerted tumorigenic, angiogenic and immunomodulatory properties, and AND-C4 was effective in antagonizing all these actions. In vivo studies in rodent glioblastoma models revealed that AND-C4 selectively bound to tumor tissue and exhibited significant efficacy on tumor growth and animal survival.

conclusionThis study represents the first evidence on the presence, origin and pro-tumoral activity of EV-3 in human glioblastoma. Moreover, in vitro and in vivo results revealed AND-C4 as novel and promising anti-glioblastoma immunotherapeutic.

Indexed as

Antibodies, MonoclonalBrain NeoplasmsErythropoietinGlioblastomaAnimalsCell Line, TumorCell ProliferationFemaleHumansImmunotherapyMiceXenograft Model Antitumor AssaysAntibodies, MonoclonalEPO protein, humanErythropoietinCancer immunotherapyCancer stem cellsErythropoietinEV-3GlioblastomaHypoxiaMonoclonal antibodiesTumor microenvironment

Identifiers

PMID41449467
PMCPMC13067427

What Socratic holds

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LicenceCC BY
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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 Socratic graph.