The Journal of Clinical Investigation (Jun 2023)

Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors

  • Agnes Bonifacius,
  • Britta Lamottke,
  • Sabine Tischer-Zimmermann,
  • Rebecca Schultze-Florey,
  • Lilia Goudeva,
  • Hans-Gert Heuft,
  • Lubomir Arseniev,
  • Rita Beier,
  • Gernot Beutel,
  • Gunnar Cario,
  • Birgit Fröhlich,
  • Johann Greil,
  • Leo Hansmann,
  • Justin Hasenkamp,
  • Michaela Höfs,
  • Patrick Hundsdoerfer,
  • Edgar Jost,
  • Kinan Kafa,
  • Oliver Kriege,
  • Nicolaus Kröger,
  • Stephan Mathas,
  • Roland Meisel,
  • Michaela Nathrath,
  • Mervi Putkonen,
  • Sarina Ravens,
  • Hans Christian Reinhardt,
  • Elisa Sala,
  • Martin G. Sauer,
  • Clemens Schmitt,
  • Roland Schroers,
  • Nina Kristin Steckel,
  • Ralf Ulrich Trappe,
  • Mareike Verbeek,
  • Daniel Wolff,
  • Rainer Blasczyk,
  • Britta Eiz-Vesper,
  • Britta Maecker-Kolhoff

Journal volume & issue
Vol. 133, no. 12

Abstract

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BACKGROUND Adoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications.METHODS We provide results of a personalized T cell manufacturing program evaluating donor, patient, T cell product, and outcome data. Patient-tailored clinical-grade EBV-specific cytotoxic T lymphocyte (EBV-CTL) products from stem cell donors (SCDs), related third-party donors (TPDs), or unrelated TPDs from the allogeneic T cell donor registry (alloCELL) at Hannover Medical School were manufactured by immunomagnetic selection using a CliniMACS Plus or Prodigy device and the EBV PepTivators EBNA-1 and Select. Consecutive manufacturing processes were evaluated, and patient outcome and side effects were retrieved by retrospective chart analysis.RESULTS Forty clinical-grade EBV-CTL products from SCDs, related TPDs, or unrelated TPDs were generated for 37 patients with refractory EBV infections or EBV-associated malignancies with and without a history of transplantation, within 5 days (median) after donor identification. Thirty-four patients received 1–14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to a complete response in 20 of 29 patients who were evaluated for clinical response. No infusion-related toxicity was reported. EBV-specific T cells in patients’ blood were detectable in 16 of 18 monitored patients (89%) after transfer, and their presence correlated with clinical response.CONCLUSION Personalized clinical-grade manufacture of EBV-CTL products via immunomagnetic selection from SCDs, related TPDs, or unrelated TPDs in a timely manner is feasible. Overall, EBV-CTLs were clinically effective and well tolerated. Our data suggest EBV-CTL transfer as a promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT, as well as patients with preexisting organ dysfunction.TRIAL REGISTRATION Not applicable.FUNDING This study was funded in part by the German Research Foundation (DFG, 158989968/SFB 900), the Deutsche Kinderkrebsstiftung (DKS 2013.09), Wilhelm-Sander-Stiftung (reference 2015.097.1), Ellen-Schmidt-Program of Hannover Medical School, and German Federal Ministry of Education and Research (reference 01EO0802).

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