Evidence map›Paper›PMID 39563035›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

ARI0003: Co-transduced CD19/BCMA dual-targeting CAR-T cells for the treatment of non-Hodgkin lymphoma.

Mireia Bachiller, Nina Barceló-Genestar, Alba Rodriguez-Garcia, Leticia Alserawan, Cèlia Dobaño-López, Marta Giménez-Alejandre, Joan Castellsagué, Salut Colell, Marc Otero-Mateo, Asier Antoñana-Vildosola and 13 more

Registry-linked trialAbstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06097455 (First in Human, Pilot, Open-label, Prospective, Multicentre, Non-randomised Clinical Trial to Evaluate the Safety and Efficacy of ARI0003), which is not on this map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing 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.

NCT06097455 early_phase1not yet recruitingnot on this map

First in Human, Pilot, Open-label, Prospective, Multicentre, Non-randomised Clinical Trial to Evaluate the Safety and Efficacy of ARI0003 (CART CD19/ CD269 Cells) in Patients With Relapsed/Refractory B-cell Aggressive Lymphoma

TypeinterventionalSponsorFundacion Clinic per a la Recerca BiomédicaRan2024 to 2027Enrolled40ConditionsRefractory Non-Hodgkin Lymphoma, Relapsed Non-Hodgkin LymphomaArmsARI0003
3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Review
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  15. Review
  16. CD19-ReTARGCancers · 2025
    Article
  17. Targets for CAR Therapy in Multiple Myeloma.International journal of molecular sciences · 2025
    Review
  18. Review
  19. Article
  20. Choosing the right double-barreled gun: ARI0003 takes aim at lymphoma by targeting both CD19 and BCMA.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
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

23 authors.

Mireia BachillerFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Nina Barceló-GenestarFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Alba Rodriguez-GarciaFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Leticia AlserawanDepartment of Immunology, Hospital Clínic, 08036 Barcelona, Spain.
Cèlia Dobaño-LópezFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red-Oncología (CIBERONC), 28029 Madrid, Spain.
Marta Giménez-AlejandreFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Joan CastellsaguéFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Salut ColellFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Marc Otero-MateoFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Asier Antoñana-VildosolaFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain.
Marta Español-RegoFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Department of Immunology, Hospital Clínic, 08036 Barcelona, Spain.
Noelia FerruzCentre for Genomic Regulation (CRG), Barcelona Institute for Science and Technology, 08003 Barcelona, Spain.
Mariona PascalFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Department of Immunology, Hospital Clínic, 08036 Barcelona, Spain; University of Barcelona, 08034 Barcelona, Spain.
Beatriz Martín-AntonioFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Instituto de Salud Carlos III, 28029 Madrid, Spain.
Xavier M AnguelaEstuary Biotherapeutics, Philadelphia, PA 19104, USA.
Cristina FillatFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Centro de Investigación en Red-Enfermedades Raras (CIBERER), 08036 Barcelona, Spain.
Eulàlia OlestiFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; University of Barcelona, 08034 Barcelona, Spain; Department of Clinical Pharmacology, Hospital Clínic, 08036 Barcelona, Spain.
Gonzalo CalvoFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; University of Barcelona, 08034 Barcelona, Spain; Department of Clinical Pharmacology, Hospital Clínic, 08036 Barcelona, Spain.
Manel JuanFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Department of Immunology, Hospital Clínic, 08036 Barcelona, Spain.
Julio DelgadoFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red-Oncología (CIBERONC), 28029 Madrid, Spain; University of Barcelona, 08034 Barcelona, Spain; Department of Hematology, Hospital Clínic, 08036 Barcelona, Spain.
Patricia Pérez-GalánFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; Centro de Investigación Biomédica en Red-Oncología (CIBERONC), 28029 Madrid, Spain.
Álvaro Urbano-IspizuaFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain; University of Barcelona, 08034 Barcelona, Spain; Department of Hematology, Hospital Clínic, 08036 Barcelona, Spain.
Sonia GuedanFundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi Sunyer (FRCB-IDIBAPS), 08036 Barcelona, Spain. Electronic address: sguedan@recerca.clinic.cat.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CD19 CAR-T therapy has achieved remarkable responses in relapsed/refractory non-Hodgkin lymphoma (NHL). However, challenges persist, with refractory responses or relapses after CAR-T administration linked to CD19 loss or downregulation. Given the co-expression of CD19 and BCMA in NHL, we hypothesized that dual targeting could enhance long-term efficacy. We optimized different dual-targeting approaches, including co-transduction of two lentiviral vectors, bicistronic, tandem, and loop and pool strategies, based on our academic anti-CD19 (ARI0001) and anti-BCMA (ARI0002h) CAR-T cells. Comparison with anti-CD19/CD20 or anti-CD19/CD22 dual targeting was also performed. We demonstrate that anti-CD19/BCMA CAR-T cells can be effectively generated through the co-transduction of two lentiviral vectors after optimization to minimize competition for cellular resources. Co-transduced T cells, called ARI0003, effectively targeted NHL tumor cells with high avidity, outperforming anti-CD19 CAR-T cells and other dual-targeting approaches both in vitro and in vivo, particularly in low CD19 antigen density models. ARI0003 maintained effectiveness post-CD19 CAR-T treatment in xenograft models and in spheroids from relapsed CART-treated patients. ARI0003 CAR-T cells were effectively manufactured under Good Manufacturing Practice conditions, with a reduced risk of genotoxicity compared to other dual-targeting approaches. A first-in-human phase 1 clinical trial (CARTD-BG-01; this study was registered at ClinicalTrials.gov [NCT06097455]) has been initiated to evaluate the safety and efficacy of ARI0003 in NHL.

Indexed as

Antigens, CD19Genetic VectorsImmunotherapy, AdoptiveLentivirusLymphoma, Non-HodgkinReceptors, Chimeric AntigenTransduction, GeneticXenograft Model Antitumor AssaysAnimalsCell Line, TumorClinical Trials, Phase I as TopicDisease Models, AnimalFemaleHumansMaleMiceAntigens, CD19CD19 molecule, humanReceptors, Chimeric AntigenCAR-T cellsco-transductiondual targetinglymphoma

Identifiers

PMID39563035
PMCPMC11764334

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Registered trials

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.