Title |
Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts
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Published in |
Journal of Translational Medicine, May 2018
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DOI | 10.1186/s12967-018-1498-3 |
Pubmed ID | |
Authors |
Regina Gary, Michael Aigner, Stephanie Moi, Stefanie Schaffer, Anja Gottmann, Stefanie Maas, Robert Zimmermann, Jürgen Zingsem, Julian Strobel, Andreas Mackensen, Josef Mautner, Andreas Moosmann, Armin Gerbitz |
Abstract |
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. 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. 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. 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. |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 26 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 31% |
Other | 3 | 12% |
Student > Ph. D. Student | 3 | 12% |
Student > Doctoral Student | 2 | 8% |
Student > Master | 2 | 8% |
Other | 1 | 4% |
Unknown | 7 | 27% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 6 | 23% |
Immunology and Microbiology | 4 | 15% |
Biochemistry, Genetics and Molecular Biology | 3 | 12% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Agricultural and Biological Sciences | 1 | 4% |
Other | 2 | 8% |
Unknown | 9 | 35% |