Evidence map›Paper›PMID 42063173›Full record

ArticleStem cell research & therapy2026

CAR-T cells targeting fibroblast activation protein eliminate pathological fibroblasts and preserve cardiac function in a Duchenne Muscular Dystrophy murine model.

Céline Marigny, Gaëlle Revet, Anne Berger, Morgane Boulch, Nathalie Mougenot, Zhenlin Li, Béatrice Corre, Mégane Lemaitre, Axelle Bois, Clara Castelli and 12 more

Abstract read
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Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

22 authors.

Céline MarignyINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Gaëlle RevetInstitut de Biologie Paris-Seine (IBPS), CNRS UMR 8263, Inserm U1345, Development, Adaptation and Ageing, Sorbonne Université, 7, quai St Bernard (case 256), 75005, Paris, France.
Anne BergerINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Morgane BoulchDynamics of Immune Responses Unit, Institut Pasteur, Université Paris Cité, INSERM U1223, Paris, France.
Nathalie MougenotSorbonne Université, UMS28, Plateforme d'Expérimentation Cœur, Muscles, Vaisseaux, Paris, France.
Zhenlin LiInstitut de Biologie Paris-Seine (IBPS), CNRS UMR 8263, Inserm U1345, Development, Adaptation and Ageing, Sorbonne Université, 7, quai St Bernard (case 256), 75005, Paris, France.
Béatrice CorreDynamics of Immune Responses Unit, Institut Pasteur, Université Paris Cité, INSERM U1223, Paris, France.
Mégane LemaitreSorbonne Université, UMS28, Plateforme d'Expérimentation Cœur, Muscles, Vaisseaux, Paris, France.
Axelle BoisINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Clara CastelliINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Victor CollombatInstitut de Biologie Paris-Seine (IBPS), CNRS UMR 8263, Inserm U1345, Development, Adaptation and Ageing, Sorbonne Université, 7, quai St Bernard (case 256), 75005, Paris, France.
Ara ParlakianInstitut de Biologie Paris-Seine (IBPS), CNRS UMR 8263, Inserm U1345, Development, Adaptation and Ageing, Sorbonne Université, 7, quai St Bernard (case 256), 75005, Paris, France.
Marie-Cécile PerierINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Adrian BotCapstan Therapeutics, San Diego, CA, USA.
Jonathan A EpsteinDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Peggy LafusteIMRB, Inserm U955-Team Relaix, Université Paris Est-Créteil, Créteil, France.
Albert HagegeINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Haig AghajanianCapstan Therapeutics, San Diego, CA, USA.
Clément CochainINSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France.
Philippe BoussoDynamics of Immune Responses Unit, Institut Pasteur, Université Paris Cité, INSERM U1223, Paris, France.
Onnik Agbulut *Institut de Biologie Paris-Seine (IBPS), CNRS UMR 8263, Inserm U1345, Development, Adaptation and Ageing, Sorbonne Université, 7, quai St Bernard (case 256), 75005, Paris, France. onnik.agbulut@sorbonne-universite.fr.
Philippe Menasché *INSERM UMRS 970, Paris Centre de Recherche Cardiovasculaire (PARCC), Univ Paris-Cité, Paris, France. philippe.menasche@aphp.fr.

Funding

Agence Nationale de la Recherche ANR-23-CPJ1-0134-01German Research Foundation 453989101Labex Revive ANR-10-LABX-73
6 · The paper itself

Abstract

backgroundChimeric Antigen Receptor (CAR)-T cells therapy has revolutionized the treatment of hematological cancers and are currently redirected towards non-malignant diseases. If correction of the gene defect remains the cornerstone of the treatment of Duchenne Muscular Dystrophy (DMD), the disease-associated fibrosis can limit its efficacy. We thus assessed the effects of eliminating cardiac fibrosis of DMD by CAR-T cells targeting Fibroblast Activation Protein (FAP), a protein strongly expressed by activated fibroblasts.

methodsIn vitro CAR-T cells expressing both FAP and a green fluorescent probe (GFP) were first co-cultured with FAP + of FAP- target cells to check for FAP-expressing lymphocyte activation. Then, anti-FAP CAR-T cells were intravenously delivered in a dystrophic murine model (D2.mdx), following lymphodepletion, to investigate the kinetics, biodistribution, cardiac functional and anti-fibrotic effects of anti-FAP CAR-T cells compared with control lymphocytes engineered to only express GFP. The mechanism of action at a cellular level was assessed by single-cell RNA-sequencing of harvested hearts.

resultsIn vitro anti-FAP CAR-T cells were successfully activated when co-cultured with FAP + target cells. In a dystrophic murine model (D2.mdx), anti-FAP CAR-T cells, intravenously delivered following lymphodepletion, homed to the heart and skeletal muscles, where they decreased FAP and fibrosis-associated genes. Single-cell RNA-sequencing linked these changes to a decrease in a definite cluster of fibrogenic fibroblasts. Concomitantly, anti-FAP CAR-T cells improved cardiac function compared to control mice injected with GFP-transduced T lymphocytes or bovine serum albumin used as negative controls.

conclusionsThese results suggest that anti-FAP CAR-T cells could be efficient for mitigating fibrosis and thus complement gene therapy of DMD. More generally, their therapeutic benefits pave the way for potential applications extending to other fibrosis-associated diseases.

Indexed as

FibroblastsGelatinasesMembrane ProteinsMuscular Dystrophy, DuchenneReceptors, Chimeric AntigenSerine EndopeptidasesT-LymphocytesAnimalsDisease Models, AnimalEndopeptidasesFibroblast Activation Protein AlphaFibrosisHumansMaleMiceMice, Inbred mdxEndopeptidasesFibroblast Activation Protein AlphaGelatinasesMembrane ProteinsReceptors, Chimeric AntigenSerine EndopeptidasesCAR-T cellsCell therapyDuchenne Muscular DystrophyFibroblast Activation ProteinFibrosis

Identifiers

PMID42063173
PMCPMC13277170

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