Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation
Amadeus T Heinz,
Friso G.J. Calkoen,
Alexander Derbich,
Lea Miltner,
Christian Seitz,
Michaela Doering,
Christiane Braun,
Daniel Atar,
Michael Schumm,
Florian Heubach,
Anne-Marie Arendt,
Ansgar Schulz,
Friedhelm R Schuster,
Roland Meisel,
Brigitte Strahm,
Juergen Finke,
Beatrice Heineking,
Susanne Stetter,
Gerda Silling,
Daniel Stachel,
Bernd Gruhn,
Klaus-Michael Debatin,
Juergen Foell,
Johannes H Schulte,
Wilhelm Woessmann,
Christine Mauz-Körholz,
Johanna Tischer,
Tobias Feuchtinger,
Rupert Handgretinger,
Peter Lang
Affiliations
Amadeus T Heinz
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Friso G.J. Calkoen
Princess Máxima Center, 3584 CS Utrecht
Alexander Derbich
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Lea Miltner
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Christian Seitz
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Michaela Doering
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Christiane Braun
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Daniel Atar
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Michael Schumm
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Florian Heubach
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Anne-Marie Arendt
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Ansgar Schulz
Department of Pediatrics, University Medical Center Ulm, Ulm
Friedhelm R Schuster
Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf
Roland Meisel
Division of Pediatric Stem Cell Therapy, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Duesseldorf
Brigitte Strahm
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, Medical Center, Faculty of Medicine, University of Freiburg
Juergen Finke
Department of Hematology and Oncology, University Hospital Freiburg, Freiburg
Beatrice Heineking
Department of Pediatric Cardiology and Intensive Care Medicine, Ludwig-Maximilians-University, Munich
Susanne Stetter
Department of Medicine III, University Hospital Regensburg, Regensburg
Gerda Silling
Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, RWTH Aachen University, Aachen
Daniel Stachel
Hospital for Pediatric and Adolescent Medicine, University of Erlangen, Erlangen
Bernd Gruhn
Department of Pediatrics, Jena University Hospital, Jena
Klaus-Michael Debatin
Department of Pediatrics, University Medical Center Ulm, Ulm
Juergen Foell
Department of Hematology and Oncology, University Children’s Hospital Regensburg, Regensburg
Johannes H Schulte
Department of Pediatric Oncology and Hematology, Charité University Medicine, Berlin
Wilhelm Woessmann
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen
Christine Mauz-Körholz
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany; Medical Faculty of the Martin-Luther-University of Halle-Wittenberg, Halle
Johanna Tischer
Department of Medicine III, Ludwig-Maximilians-University, Munich
Tobias Feuchtinger
Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner University Children’s Hospital, Munich
Rupert Handgretinger
Abu Dhabi Stem Cells Center, Al Misaha Street, Rowdhat, Abu Dhabi, UAE
Peter Lang
Department of Pediatric Hematology and Oncology, University Children’s Hospital Tübingen, Tübingen
Therapy-resistant viral reactivations contribute significantly to mortality after hematopoietic stem cell transplantation. Adoptive cellular therapy with virus-specific T cells (VST) has shown efficacy in various single-center trials. However, the scalability of this therapy is hampered by laborious production methods. In this study we describe the in-house production of VST in a closed system (CliniMACS Prodigy® system, Miltenyi Biotec). In addition, we report the efficacy in 26 patients with viral disease following hematopoietic stem cell transplantation in a retrospective analysis (adenovirus, n=7; cytomegalovirus, n=8; Epstein-Barr virus, n=4; multi-viral, n=7). The production of VST was successful in 100% of cases. The safety profile of VST therapy was favorable (n=2 grade 3 and n=1 grade 4 adverse events; all three were reversible). A response was seen in 20 of 26 patients (77%). Responding patients had a significantly better overall survival than patients who did not respond (P<0.001). Virus-specific symptoms were reduced or resolved in 47% of patients. The overall survival of the whole cohort was 28% after 6 months. This study shows the feasibility of automated VST production and safety of application. The scalability of the CliniMACS Prodigy® device increases the accessibility of VST treatment.
