Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation

Br J Haematol. 2006 Jul;134(1):64-76. doi: 10.1111/j.1365-2141.2006.06108.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus Infections, Human / immunology
  • Adenovirus Infections, Human / therapy*
  • Adenoviruses, Human / immunology*
  • Adoptive Transfer / methods*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Cell Separation / methods
  • Child
  • Child, Preschool
  • Feasibility Studies
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Infant
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology*
  • Transplantation, Homologous
  • Treatment Outcome