Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts
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 tra...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12967-018-1498-3 |
| _version_ | 1818067610259947520 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Regina Gary |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T15:26:25Z |
| format | Article |
| id | doaj.art-02209ab18ee1414686a909d1b6cd75c0 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-10T15:26:25Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-02209ab18ee1414686a909d1b6cd75c02022-12-22T01:43:31ZengBMCJournal of Translational Medicine1479-58762018-05-0116111510.1186/s12967-018-1498-3Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell graftsRegina Gary0Michael Aigner1Stephanie Moi2Stefanie Schaffer3Anja Gottmann4Stefanie Maas5Robert Zimmermann6Jürgen Zingsem7Julian Strobel8Andreas Mackensen9Josef Mautner10Andreas Moosmann11Armin Gerbitz12Dept. of Hematology/Oncology, University Hospital of ErlangenDept. of Hematology/Oncology, University Hospital of ErlangenDept. of Hematology/Oncology, University Hospital of ErlangenDept. of Hematology/Oncology, University Hospital of ErlangenDept. of Hematology/Oncology, University Hospital of ErlangenCenter for Clinical Studies CCS, University Hospital of ErlangenDepartment of Transfusion Medicine and Hemostaseology, University Hospital of ErlangenDepartment of Transfusion Medicine and Hemostaseology, University Hospital of ErlangenDepartment of Transfusion Medicine and Hemostaseology, University Hospital of ErlangenDept. of Hematology/Oncology, University Hospital of ErlangenClinical Cooperation Group Pediatric Tumor Immunology, Helmholtz Zentrum München, and Technical University of MunichDZIF Research Group Host Control of Viral Latency and Reactivation (HOCOVLAR), Helmholtz Zentrum MünchenDepartment of Hematology, Oncology and Tumorimmunology, Charité BerlinAbstract 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.http://link.springer.com/article/10.1186/s12967-018-1498-3Stem cell transplantationAllogeneicCMVEBVReactivationT cell |
| spellingShingle | 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 Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts Journal of Translational Medicine Stem cell transplantation Allogeneic CMV EBV Reactivation T cell |
| title | Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts |
| title_full | Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts |
| title_fullStr | Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts |
| title_full_unstemmed | Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts |
| title_short | Clinical-grade generation of peptide-stimulated CMV/EBV-specific T cells from G-CSF mobilized stem cell grafts |
| title_sort | clinical grade generation of peptide stimulated cmv ebv specific t cells from g csf mobilized stem cell grafts |
| topic | Stem cell transplantation Allogeneic CMV EBV Reactivation T cell |
| url | http://link.springer.com/article/10.1186/s12967-018-1498-3 |
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