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

Item Type:Article
Title:Patient-tailored adoptive immunotherapy with EBV-specific T cells from related and unrelated donors
Creators Name:Bonifacius, A. and Lamottke, B. and Tischer-Zimmermann, S. and Schultze-Florey, R. and Goudeva, L. and Heuft, H.G. and Arseniev, L. and Beier, R. and Beutel, G. and Cario, G. and Fröhlich, B. and Greil, J. and Hansmann, L. and Hasenkamp, J. and Höfs, M. and Hundsdoerfer, P. and Jost, E. and Kafa, K. and Kriege, O. and Kröger, N. and Mathas, S. and Meisel, R. and Nathrath, M. and Putkonen, M. and Ravens, S. and Reinhardt, H.C. and Sala, E. and Sauer, M.G and Schmitt, C. and Schroers, R. and Steckel, N.K. and Trappe, R.U. and Verbeek, M. and Wolff, D. and Blasczyk, R. and Eiz-Vesper, B. and Maecker-Kolhoff, B.
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.
Source:Journal of Clinical Investigation
ISSN:0021-9738
Publisher:American Society for Clinical Investigation
Page Range:e163548
Date:9 May 2023
Official Publication:https://doi.org/10.1172/JCI163548
PubMed:View item in PubMed

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