Evidence map›Paper›PMID 42218471›Full record

ArticleJournal of translational medicine2026

A brain-penetrant chimeric protein combines direct glioma targeting with myeloid cell-mediated immune reprogramming.

Elisabetta Mori, Elisa De Santis, Marta Scalera, Julia Meissel, Elena Ellmeier, Alessandra Flori, Luca Menichetti, Gudula Schmidt, Antonino Cattaneo, Stefano Angiari and 2 more

Abstract read
In one paragraph

Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Elisabetta MoriBio@SNS, Scuola Normale Superiore, 56124, Pisa, Italy.
Elisa De SantisBio@SNS, Scuola Normale Superiore, 56124, Pisa, Italy.
Marta ScaleraCNR Institute of Neuroscience, 56124, Pisa, Italy.
Julia MeisselDivision of Immunology, Otto Loewi Research Center, Medical University of Graz, Graz, 8010, Austria.
Elena EllmeierDivision of Immunology, Otto Loewi Research Center, Medical University of Graz, Graz, 8010, Austria.
Alessandra FloriBioengineering Unit, "G. Monasterio" Foundation - Regione Toscana, CNR, 56124, Pisa, Italy.
Luca MenichettiCNR Institute of Clinical Physiology, 56124, Pisa, Italy.
Gudula SchmidtMedizinische Fakultät, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, University of Freiburg, 79104, Freiburg, Germany.
Antonino CattaneoBio@SNS, Scuola Normale Superiore, 56124, Pisa, Italy.
Stefano AngiariDivision of Immunology, Otto Loewi Research Center, Medical University of Graz, Graz, 8010, Austria.
Mario CostaCNR Institute of Neuroscience, 56124, Pisa, Italy.
Eleonora VanniniCNR Institute of Neuroscience, 56124, Pisa, Italy. eleonora.vannini@in.cnr.it.ORCID http://orcid.org/0000-0002-1337-3901

Funding

Associazione Italiana per la Ricerca sul Cancro Grant #IG30434Associazione Italiana per la Ricerca sul Cancro My First AIRC Grant 2022 #ID27254Ministero dell'Istruzione, dell'Università e della Ricerca PRIN MIUR 2020 #2020Z73J5A
6 · The paper itself

Abstract

backgroundGlioblastoma (GB) is the most aggressive primary brain tumor, characterized by poor prognosis, profound immunosuppression, and limited response to current therapies. To overcome these barriers, we developed CTX-CNF1, a brain-penetrant recombinant protein that integrates direct glioma targeting with myeloid cell-mediated immune reprogramming.

methodsCTX-CNF1 was generated by fusing Chlorotoxin (CTX), which enables selective delivery across the blood-brain barrier, with Cytotoxic Necrotizing Factor 1 (CNF1), a bacterial protein with antitumor and immunostimulatory properties. Therapeutic efficacy was evaluated in immunocompetent orthotopic GB mouse models using survival analysis, MRI, motor assessment, and immunophenotyping.

resultsSystemic CTX-CNF1 administration was well tolerated and significantly prolonged survival, reduced tumor burden, and preserved motor function. A substantial proportion of treated animals achieved complete tumor regression and resisted tumor re-challenge, consistent with the induction of durable antitumor immunity. Mechanistically, CTX-CNF1 promoted a pro-inflammatory reprogramming of tumor-associated myeloid cells and enhanced CD8⁺ T-cell recruitment and cytotoxicity, thereby counteracting GB-associated immunosuppression. Therapeutic efficacy was confirmed across distinct glioma models. In combination settings, CTX-CNF1 selectively enhanced the activity of immune checkpoint blockade in a context-dependent manner.

conclusionsCTX-CNF1 represents a dual-action therapeutic strategy that combines tumor targeting with immune modulation and effective brain delivery. By coupling direct antitumor effects with remodeling of the tumor immune microenvironment, CTX-CNF1 supports the development of combinatorial approaches to overcome therapeutic resistance in GB and other immune-cold tumors.

Indexed as

BrainBrain NeoplasmsCellular ReprogrammingGliomaMyeloid CellsRecombinant Fusion ProteinsAnimalsCD8-Positive T-LymphocytesCell Line, TumorHumansMiceRecombinant Fusion ProteinsCD8+ T cellsCTX-CNF1GlioblastomaImmunotherapyMurine modelsMyeloid cellsRecombinant proteinsTranslational oncologyTumor microenvironment

Identifiers

PMID42218471
PMCPMC13435415

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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.