title: Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation.
abstract: During periods of immunosuppression, such as postallogeneic stem cell transplantation (SCT), patients are at significant risk for severe viral infections. Human adenovirus (HAdV) infection is a serious complication post-SCT, especially in children. Virus-specific T cells are essential for the clearance of HAdV, as antiviral chemotherapy has revealed limited success. We present feasibility data for a new treatment option using virus-specific donor T cells for adoptive transfer of immunity to patients with HAdV-infection/reactivation. Virus-specific donor T cells were isolated and infused into nine children with systemic HAdV infection after SCT. Isolation was based on gamma-interferon (IFN-gamma) secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4(+) and CD8(+) T cells. 1.2-50 x 10(3)/kg T cells were infused for adoptive transfer. Isolated cells showed high specificity and markedly reduced alloreactivity in vitro. Adoptive transfer of HAdV-specific immunity was successful in five of six evaluable patients, documented by a dose-independent and sustained in vivo expansion of HAdV-specific T cells, associated with a durable clearance/decrease of viral copies. T-cell infusion was well tolerated in all nine patients, except one case with graft-versus-host disease II of the skin. In conclusion, induction of a specific T-cell response through adoptive transfer was feasible and effective. When performed early in the course of infection, adoptive T-cell transfer may protect from HAdV-related complications.
authors.affiliation: Department of Paediatric Haematology/Oncology, University Children's Hospital, Eberhard-Karls-University, Tuebingen, Germany. tobias.feuchtinger@med.uni-tuebingen.de
authors.forename: Tobias
authors.initials: T
authors.lastname: Feuchtinger
authors.forename: Susanne
authors.initials: S
authors.lastname: Matthes-Martin
authors.forename: Celine
authors.initials: C
authors.lastname: Richard
authors.forename: Thomas
authors.initials: T
authors.lastname: Lion
authors.forename: Monika
authors.initials: M
authors.lastname: Fuhrer
authors.forename: Klaus
authors.initials: K
authors.lastname: Hamprecht
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Christina
authors.initials: C
authors.lastname: Peters
authors.forename: Friedhelm R
authors.initials: FR
authors.lastname: Schuster
authors.forename: Robert
authors.initials: R
authors.lastname: Beck
authors.forename: Michael
authors.initials: M
authors.lastname: Schumm
authors.forename: Ramin
authors.initials: R
authors.lastname: Lotfi
authors.forename: Gerhard
authors.initials: G
authors.lastname: Jahn
authors.forename: Peter
authors.initials: P
authors.lastname: Lang
mesh_terms: D000258:Adenovirus Infections, Human / Q000276:immunology / Q000628:therapy*; D000260:Adenoviruses, Human / Q000276:immunology*; D019264:Adoptive Transfer / Q000379:methods*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*; D014184:Transplantation, Homologous; D016896:Treatment Outcome