Automated production of specific T cells for treatment of refractory viral infections after allogeneic stem cell transplantation

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...

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Published in:Haematologica (Roma) 2023-08, Vol.108 (8), p.2080-2090
Main Authors: Heinz, Amadeus T, Calkoen, Friso G J, Derbich, Alexander, Miltner, Lea, Seitz, Christian, Doering, Michaela, Braun, Christiane, Atar, Daniel, Schumm, Michael, Heubach, Florian, Arendt, Anne-Marie, Schulz, Ansgar, Schuster, Friedhelm R, Meisel, Roland, Strahm, Brigitte, Finke, Juergen, Heineking, Beatrice, Stetter, Susanne, Silling, Gerda, Stachel, Daniel, Gruhn, Bernd, Debatin, Klaus-Michael, Foell, Juergen, Schulte, Johannes H, Woessmann, Wilhelm, Mauz-Körholz, Christine, Tischer, Johanna, Feuchtinger, Tobias, Handgretinger, Rupert, Lang, Peter
Format: Article
Language:English
Subjects:
Cell Therapy & Immunotherapy
Epstein-Barr Virus Infections - therapy
Hematopoietic Stem Cell Transplantation - adverse effects
Herpesvirus 4, Human
Humans
Immunotherapy, Adoptive - adverse effects
Immunotherapy, Adoptive - methods
Retrospective Studies
Stem Cell Transplantation
T-Lymphocytes
Virus Diseases - etiology
Virus Diseases - therapy
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Summary: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
ISSN:0390-6078
1592-8721
DOI:10.3324/haematol.2022.281996