Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts

dc.contributor.authorGary, Regina
dc.contributor.authorAigner, Michael
dc.contributor.authorMoi, Stephanie
dc.contributor.authorSchaffer, Stefanie
dc.contributor.authorGottmann, Anja
dc.contributor.authorMaas, Stefanie
dc.contributor.authorZimmermann, Robert
dc.contributor.authorZingsem, Jürgen
dc.contributor.authorStrobel, Julian
dc.contributor.authorMackensen, Andreas
dc.contributor.authorMautner, Josef
dc.contributor.authorMoosmann, Andreas
dc.contributor.authorGerbitz, Armin
dc.date.accessioned2018-05-22
dc.date.available2018-05-15
dc.date.created2018
dc.date.issued2018-05-22
dc.description.abstractBackground A major complication after allogeneic hematopoietic stem cell transplantation (aSCT) is the reactivation of herpesviruses such as cytomegalovirus (CMV) and Epstein–Barr virus (EBV). Both viruses cause significant mortality and compromise quality of life after aSCT. Preventive transfer of virus-specific T cells can suppress reactivation by re-establishing functional antiviral immune responses in immunocompromised hosts. Methods We have developed a good manufacturing practice protocol to generate CMV/EBV-peptide-stimulated T cells from leukapheresis products of G-CSF mobilized and non-mobilized donors. Our procedure selectively expands virus-specific CD8+ und CD4+ T cells over 9 days using a generic pool of 34 CMV and EBV peptides that represent well-defined dominant T-cell epitopes with various HLA restrictions. For HLA class I, this set of peptides covers at least 80% of the European population. Results CMV/EBV-specific T cells were successfully expanded from leukapheresis material of both G-CSF mobilized and non-mobilized donors. The protocol allows administration shortly after stem cell transplantation (d30+), storage over liquid nitrogen for iterated applications, and protection of the stem cell donor by avoiding a second leukapheresis. Conclusion Our protocol allows for rapid and cost-efficient production of T cells for early transfusion after aSCT as a preventive approach. It is currently evaluated in a phase I/IIa clinical trial.en
dc.identifier.citationJournal of Translational Medicine 16 (2018). <https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-018-1498-3>
dc.identifier.doihttps://doi.org/10.1186/s12967-018-1498-3
dc.identifier.opus-id9729
dc.identifier.urihttps://open.fau.de/handle/openfau/9729
dc.identifier.urnurn:nbn:de:bvb:29-opus4-97299
dc.language.isoen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/deed.de
dc.subjectStem cell transplantation
dc.subjectAllogeneic
dc.subjectCMV
dc.subjectEBV
dc.subjectReactivation
dc.subjectT cell
dc.subjectAdoptive transfer
dc.subject.ddcDDC Classification::6 Technik, Medizin, angewandte Wissenschaften :: 61 Medizin und Gesundheit :: 610 Medizin und Gesundheit
dc.titleClinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell graftsen
dc.typearticle
dcterms.publisherFriedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
local.journal.titleJournal of Translational Medicine
local.journal.volume16
local.sendToDnbfree*
local.subject.fakultaetMedizinische Fakultät
local.subject.gnd-
local.subject.sammlungUniversität Erlangen-Nürnberg / Open Access Artikel ohne Förderung / Open Access Artikel ohne Förderung 2018
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