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

Gary R, Aigner M, Moi S, Schaffer S, Gottmann A, Maas S, Zimmermann R, Zingsem J, Strobel J, Mackensen A, Mautner J, Moosmann A, Gerbitz A (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Book Volume: 16

Journal Issue: 1

DOI: 10.1186/s12967-018-1498-3

Abstract

BACKGROUND: 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.

Authors with CRIS profile

Involved external institutions

Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE) Charité - Universitätsmedizin Berlin Germany (DE)

How to cite

APA:

Gary, R., Aigner, M., Moi, S., Schaffer, S., Gottmann, A., Maas, S.,... Gerbitz, A. (2018). Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts. Journal of Translational Medicine, 16(1). https://dx.doi.org/10.1186/s12967-018-1498-3

MLA:

Gary, Regina, et al. "Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts." Journal of Translational Medicine 16.1 (2018).

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