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


  • A. Bonifacius
  • B. Lamottke
  • S. Tischer-Zimmermann
  • R. Schultze-Florey
  • L. Goudeva
  • H.G. Heuft
  • L. Arseniev
  • R. Beier
  • G. Beutel
  • G. Cario
  • B. Fröhlich
  • J. Greil
  • L. Hansmann
  • J. Hasenkamp
  • M. Höfs
  • P. Hundsdoerfer
  • E. Jost
  • K. Kafa
  • O. Kriege
  • N. Kröger
  • S. Mathas
  • R. Meisel
  • M. Nathrath
  • M. Putkonen
  • S. Ravens
  • H.C. Reinhardt
  • E. Sala
  • M.G Sauer
  • C. Schmitt
  • R. Schroers
  • N.K. Steckel
  • R.U. Trappe
  • M. Verbeek
  • D. Wolff
  • R. Blasczyk
  • B. Eiz-Vesper
  • B. Maecker-Kolhoff


  • Journal of Clinical Investigation


  • J Clin Invest 133 (12): e163548


  • 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 (SCD), related third party donors (TPD) or unrelated TPD from the allogeneic T-cell donor registry (alloCELL) established at Hannover Medical School were manufactured by immunomagnetic selection using CliniMACS Plus or Prodigy device and 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 or unrelated TPDs were generated for 37 patients with and without transplantation (Tx) history within 5 days (median) after donor identification. 34 patients received 1-14 EBV-CTL products (fresh and cryopreserved). EBV-CTL transfer led to 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 16/18 monitored patients (89 %) after transfer and correlated with clinical response. CONCLUSION: In conclusion, personalized clinical-grade manufacturing of EBV-CTL products via immunomagnetic selection from SCD, related or unrelated TPD is feasible in a timely manner. Overall, EBV-CTL were clinically effective and well-tolerated. Our data suggest EBV-CTL as promising therapeutic approach for immunocompromised patients with refractory EBV-associated diseases beyond HSCT as well as patients with pre-existing organ dysfunction.