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Publications

Journal Article Ahead of print 1 citation

PubMed: 42661098 DOI: 10.1038/s41591-026-04603-3

CD19 CAR T cell therapy for treatment-refractory seropositive rheumatoid arthritis: a phase 1 trial.

Nat Med

Authors: Fredrik N Albach, Marie C Rehm, Marie Luise Hütter-Krönke, Thanh Hang Le, Julia M Giezen, Murat Torgutalp, Arne Sattler, Ioanna Minopoulou, Robert Biesen, Edgar Wiebe, Vincent Casteleyn, Thorben Witte, Christian Furth, Jan Zernicke, Melanie Nuesch Germano, Johan Verhagen, Artur Wilhelm, Maria Dzamukova, Klaus Engel, Simon Schallenberg, Aimo Kannt, Nicole Ziegler, Michaela Fehringer, Udo Schneider, Nadine Unterwalder, Mark Beling, Alexander Pfeil, Elpida Phithak, Martin Krusche, Olaf Penack, Tobias Alexander, Werner Stenzel, Manfred Wuhrer, Kamran Movassaghi, Thomas Dörner, Eicke Latz, Thomas Vogl, Antonia Busse, Georg Schett, Hans Ulrich Scherer, Rene E M Toes, Arnd Kleyer, Ulrich Keller, Lars Bullinger, David Simon, Gerhard Krönke

Affiliations

  • Department of Rheumatology and Clinical Immunology, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Fraunhofer Institute for Translational Medicine and Pharmacology, Berlin, Germany.
  • Department of Hematology, Oncology and Cancer Immunology, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
  • Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands.
  • Department of Nuclear Medicine, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Siemens Healthineers, Erlangen, Germany.
  • Institute of Pathology, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Fraunhofer Institute for Translational Medicine and Pharmacology, Frankfurt, Germany.
  • Institute of Clinical Pharmacology, Goethe University, Frankfurt, Germany.
  • Center for Cancer Research, Medical University of Vienna, Vienna, Austria.
  • Fachbereich Autoimmundiagnostik, Labor Berlin-Charité Vivantes GmbH, Berlin, Germany.
  • Ambulatory Medical Care Center, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Department of Internal Medicine III, Center of Rheumatology and Section Rheumatology and Osteology, Jena University Hospital-Friedrich Schiller University Jena, Jena, Germany.
  • III. Department of Medicine, Division of Rheumatology and Systemic Inflammatory Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Department of Neuropathology, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
  • ImmunoPreCept Cluster of Excellence, Charité-University Medical Center Berlin, Berlin, Germany.
  • Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
  • German Cancer Consortium (DKTK), Berlin, Germany.
  • Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Department of Rheumatology and Clinical Immunology, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Fraunhofer Institute for Translational Medicine and Pharmacology, Berlin, Germany.
  • Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
  • Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Department of Rheumatology and Clinical Immunology, Charité - University Medical Center Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
  • Fraunhofer Institute for Translational Medicine and Pharmacology, Berlin, Germany.
  • Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
  • ImmunoPreCept Cluster of Excellence, Charité-University Medical Center Berlin, Berlin, Germany.
  • Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.
  • Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander University of Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Abstract

Chimeric antigen receptor (CAR) T cell-mediated B cell depletion has demonstrated efficacy in several autoimmune diseases. Here we report clinical and molecular data obtained during the nonrandomized phase 1 part of the phase 1/2 COMPARE trial, evaluating safety and efficacy of mivocabtagene autoleucel (miv-cel), an autologous fully human CD19 CAR T cell therapy, in rheumatoid arthritis (RA). Six patients (three men, three women) with severe, treatment-refractory, anti-citrullinated protein antibody (ACPA)-positive RA received a single infusion of miv-cel after stopping all disease-modifying antirheumatic drug treatments and after standard lymphodepletion therapy. Patients were followed for 36-52 weeks for safety and efficacy. Primary endpoints were the incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) and adverse events (AEs) within the first 4 weeks after treatment. Secondary and explorative endpoints assessed clinical efficacy and cellular and humoral immune responses. CRS occurred in all patients and was limited to grade 1 and 2 events. No ICANSs or serious AEs occurred; one dose-limiting toxicity was recorded (grade 3 transaminase elevation, resolved without sequelae). The primary endpoint was met with acceptable safety findings, allowing advancement to phase 2. CAR T cell therapy resulted in depletion of CD19 + B cells across blood and tissue, coinciding with a continuous decline of autoantibodies with seroconversion in four of the six patients for ACPAs against mutated citrullinated vimentin and five of six for rheumatoid factor immunoglobulin M. Despite cessation of immunosuppressive treatments, disease activity improved in all patients (median 34% DAS28-CRP reduction at the latest follow-up with DAS28-CRP remission and American College of Rheumatology 70% response in 3 of 6 patients). CD19 CAR T cells showed acceptable short-term tolerability in patients with treatment-refractory RA, justifying further evaluation. ClinicalTrials.gov identifier: NCT06475495 .

MeSH

Cells, Safety, Arthritis, Arthritis, Rheumatoid, Therapeutics, T-Lymphocytes, B-Lymphocytes, Car-T Cell