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Icheva, V.* ; Kayser, S.* ; Wolff, D.* ; Tuve, S.* ; Kyzirakos, C.* ; Bethge, W.* ; Greil, J.* ; Albert, M.H.* ; Schwinger, W.* ; Nathrath, M. ; Schumm, M.* ; Stevanovic, S.* ; Handgretinger, R.* ; Lang, P.* ; Feuchtinger, T.*

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.

J. Clin. Oncol. 31, 5-7 (2013)

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PURPOSEReactivation 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 METHODSTo 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.ResultsWe 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. CONCLUSIONAdoptive 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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