Adoptive transfer of Epstein-Barr Virus (EBV) nuclear antigen 1-specific T cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation
Purpose Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promi...
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| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2013
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| In: |
Journal of clinical oncology
Year: 2012, Volume: 31, Issue: 1, Pages: 39-48 |
| ISSN: | 1527-7755 |
| DOI: | 10.1200/JCO.2011.39.8495 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1200/JCO.2011.39.8495 Verlag, lizenzpflichtig, Volltext: https://ascopubs.org/doi/10.1200/JCO.2011.39.8495 
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| Author Notes: | Vanya Icheva, Simone Kayser, Daniel Wolff, Sebastian Tuve, Christina Kyzirakos, Wolfgang Bethge, Johann Greil, Michael H. Albert, Wolfgang Schwinger, Michaela Nathrath, Michael Schumm, Stefan Stevanovic, Rupert Handgretinger, Peter Lang, and Tobias Feuchtinger |
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| 245 | 1 | 0 | |a Adoptive transfer of Epstein-Barr Virus (EBV) nuclear antigen 1-specific T cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation |c Vanya Icheva, Simone Kayser, Daniel Wolff, Sebastian Tuve, Christina Kyzirakos, Wolfgang Bethge, Johann Greil, Michael H. Albert, Wolfgang Schwinger, Michaela Nathrath, Michael Schumm, Stefan Stevanovic, Rupert Handgretinger, Peter Lang, and Tobias Feuchtinger |
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| 520 | |a Purpose Reactivation of Epstein-Barr virus (EBV) after allogeneic stem-cell transplantation (SCT) can lead to severe life-threatening infections and trigger post-transplantation lymphoproliferative disease (PTLD). Since EBV-specific T cells could prevent PTLD, cellular immunotherapy has been a promising treatment option. However, generation of antigen-specific T-cell populations has been difficult within a short time frame. Patients and Methods To improve availability in urgent clinical conditions, we developed a rapid protocol for isolation of polyclonal EBV nuclear antigen 1 (EBNA-1) -specific T cells by using an interferon gamma (IFN-γ) capture technique. Results We report on the use of adoptive transfer of EBNA-1-specific T cells in 10 pediatric and adult patients with EBV viremia and/or PTLD after SCT. No acute toxicity or graft-versus-host disease (GVHD) of more than grade 2 occurred as a result of adoptive T-cell transfer. In vivo expansion of transferred EBNA-1-specific T cells was observed in eight of 10 patients after a median of 16 days following adoptive transfer that was associated with clinical and virologic response in seven of them (70%). None of the responders had EBV-associated mortality. Within clinical responders, three patients were disease free by the day of last follow-up (2 to 36 months), three patients died of other infectious complications, and one patient died as a result of relapse of malignancy. EBV-related mortality was observed in two of 10 patients, and another patient had ongoing viremia without clinical symptoms at last follow-up. Conclusion Adoptive ex vivo transfer of EBNA-1-specific T cells is a feasible and well-tolerated therapeutic option, representing a fast and efficient procedure to achieve reconstitution of antiviral T-cell immunity after SCT. | ||
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