Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation.
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.
Feuchtinger
Tobias
T
Department of Paediatric Haematology/Oncology, University Children's Hospital, Eberhard-Karls-University, Tuebingen, Germany. tobias.feuchtinger@med.uni-tuebingen.de
Matthes-Martin
Susanne
S
Richard
Celine
C
Lion
Thomas
T
Fuhrer
Monika
M
Hamprecht
Klaus
K
Handgretinger
Rupert
R
Peters
Christina
C
Schuster
Friedhelm R
FR
Beck
Robert
R
Schumm
Michael
M
Lotfi
Ramin
R
Jahn
Gerhard
G
Lang
Peter
P
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