title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Children's Hospital, Tübingen, Germany.
authors.forename: Vanya
authors.initials: V
authors.lastname: Icheva
authors.forename: Simone
authors.initials: S
authors.lastname: Kayser
authors.forename: Daniel
authors.initials: D
authors.lastname: Wolff
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tuve
authors.forename: Christina
authors.initials: C
authors.lastname: Kyzirakos
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bethge
authors.forename: Johann
authors.initials: J
authors.lastname: Greil
authors.forename: Michael H
authors.initials: MH
authors.lastname: Albert
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwinger
authors.forename: Michaela
authors.initials: M
authors.lastname: Nathrath
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Stefan
authors.initials: S
authors.lastname: Stevanovic
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
mesh_terms: D000293:Adolescent; D019264:Adoptive Transfer; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000150:complications* / Q000628:therapy; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D014184:Transplantation, Homologous; D019562:Viral Load / Q000276:immunology; D055815:Young Adult
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D007371:Interferon-gamma; C417029:EBV-encoded nuclear antigen 1