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

Haematologica. 2023 Aug 1;108(8):2080-2090. doi: 10.3324/haematol.2022.281996.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Grants and funding

Funding: This work was supported by grants from the excellence cluster iFIT (EXC 2180) [Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Länder – WXC 2180 – 390900677], from the Dieter Schwarz Stiftung Neckarsulm, and from the Reinhold-Beitlich Stiftung Tuebingen to PL; from the Foerderverein and from the Stiftung fuer krebskranke Kinder Tuebingen e.V. to PL and to ATH.