Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors
Authors
- 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
- Journal of Clinical Investigation
Citation
- J Clin Invest 133 (12): e163548
Abstract
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.