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

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

Bonifacius, Agnes; Lamottke, Britta; Tischer-Zimmermann, Sabine; Schultze-Florey, Rebecca; Goudeva, Lilia; Heuft, Hans-Gert; Arseniev, Lubomir; Beier, Rita; Beutel, Gernot; Cario, Gunnar; Fröhlich, Birgit; Greil, Johann; Hansmann, Leo; Hasenkamp, Justin; Höfs, Michaela; Hundsdoerfer, Patrick; Jost, Edgar; Kafa, Kinan; Kriege, Oliver; Kröger, Nicolaus; Mathas, Stephan; Meisel, Roland; Nathrath, Michaela; Putkonen, Mervi; Ravens, Sarina; Reinhardt, Hans Christian; Sala, Elisa; Sauer, Martin G; Sch...     »

BACKGROUNDAdoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications.METHODSWe 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.RESULTSForty 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.CONCLUSIONPersonalized 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 REGISTRATIONNot applicable.FUNDINGThis 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).      «

BACKGROUNDAdoptive transfer of EBV-specific T cells can restore specific immunity in immunocompromised patients with EBV-associated complications.METHODSWe 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 (alloCEL...     »