Evidence map›Paper›PMID 39903124›Full record

ArticleBlood advances2025

CD19.CAR T-cell-derived extracellular vesicles express CAR and kill leukemic cells, contributing to antineoplastic therapy.

Paola Lanuti, Francesco Guardalupi, Giulia Corradi, Rosalba Florio, Davide Brocco, Serena Veschi, Elsa Pennese, Domenico De Bellis, Francesca D'Ascanio, Anna Piro and 25 more

Abstract read
In one paragraph

Article in Blood advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. CAR-engineered neutrophils derived from induced pluripotent stem cells: a new frontier in cellular immunotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  2. Article
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  5. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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  9. CAR T cell engineering approaches to minimise toxicities.Experimental biology and medicine (Maywood, N.J.) · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Paola LanutiDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.
Francesco GuardalupiDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.
Giulia CorradiDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.ORCID 0000-0003-2585-4881
Rosalba FlorioDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-3095-1451
Davide BroccoDepartment of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0001-8634-7184
Serena VeschiDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0003-0450-9210
Elsa PenneseDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Domenico De BellisDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-0953-1989
Francesca D'AscanioDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-0588-5536
Anna PiroDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0009-0000-8076-2491
Laura De LellisDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-6460-2508
Pasquale SimeoneDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.
Maria Concetta CufaroCenter for Advanced Studies and Technology, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-6457-7795
Serena PilatoDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Isabella D'AmarioDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.
Ida VillanovaDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Barbara Di FrancescoDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Lucia Di ReDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.
Fabio VerginelliCenter for Advanced Studies and Technology, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-8636-2517
Damiana PieragostinoCenter for Advanced Studies and Technology, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0003-1015-3484
Prassede SalutariDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.ORCID 0009-0006-0064-5951
Fabrizia ColasanteDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Annalisa NataleDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Maria Vittoria MattoliDepartment of Hospital Services, Nuclear Medicine Unit, Pescara Hospital, Pescara, Italy.
Simone VespaDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0001-6146-9302
Antonella FontanaDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-5391-7520
Raffaella GiancolaDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Bianca FabiDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.ORCID 0000-0002-1290-2760
Stefano BaldoniDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.ORCID 0000-0002-5420-5672
Stella SantaroneDepartment of Oncology and Hematology, Pescara Hospital, Pescara, Italy.
Francesco RestucciaDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-4583-651X
Nicola TinariDepartment of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
Piero Del BoccioCenter for Advanced Studies and Technology, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0003-1653-2194
Alessandro CamaDepartment of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0003-3647-1368
Mauro Di IanniDepartment of Medicine and Aging Sciences, University of Chieti-Pescara, Chieti, Italy.ORCID 0000-0002-6701-4023

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractChimeric antigen receptor (CAR) T-cell-derived extracellular vesicles (EVs) might represent a new therapeutic tool for boosting CAR T-cell antileukemic effects. Here, a cohort of 22 patients who received infusion with CD19 CAR T cells were monitored for the presence of circulating CD19 CAR+ T-cell-derived EVs (CD19.CAR+EVs), which were then separated and functionally characterized for their killing abilities. A good manufacturing practice (GMP)-compliant separation method was also developed. Results demonstrated that CD19.CAR+EVs were detectable in peripheral blood up to 2 years after infusion, indicating long-lasting persistence of their parental cells. Notably, early decreases of circulating CD19.CAR+EV concentrations correlated with failure of CAR T-cell therapy. Circulating CD19.CAR+EVs displayed a median size (standard deviation) of 133.1 ± 65.5 nm and carried a proapoptotic protein cargo. These EVs expressed higher CAR levels than their parental cells. Furthermore, CD19.CAR+EVs did not activate heterologous T cells and produced significant, specific, and dose-dependent cytotoxic effects on CD19+ cell lines and primary cells. The new GMP-compliant EV isolation method allowed for a recovery of 63% ± 5.7% of CD19.CAR+EVs. A deeper analysis of the different protein cargoes carried by EVs derived from different CAR T-cell subpopulations identified a proapoptotic functional pathway linked to CD8+LAG-3+ EVs. Overall, our data indicate that CD19.CAR+EVs may be proposed as promising dynamic new biomarkers of CAR T-cell activity and, by contributing to the direct killing of leukemic targets, represent a new product with strong therapeutic potential that could be infused independently of CAR T cells.

Indexed as

Antigens, CD19Extracellular VesiclesImmunotherapy, AdoptiveLeukemiaReceptors, Chimeric AntigenT-LymphocytesCell Line, TumorCytotoxicity, ImmunologicFemaleHumansMaleMiddle AgedAntigens, CD19Receptors, Chimeric Antigen

Identifiers

PMID39903124
PMCPMC12180994

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