Use of suicide gene-expressing donor T-cells to control alloreactivity after haematopoietic stem cell transplantation

Abstract

Conditional ablation of alloreactive donor T-cells to prevent or treat graft-versus-host disease (GvHD) in the context of allogeneic haematopoietic stem cell transplantation could significantly contribute to expand the use of alloreactivity as a treatment modality. The prevention and treatment of GvHD induced by herpes simplex virus 1-thymidine kinase (HS-tk)-expressing donor T-cells by ganciclovir (GCV) has been demonstrated. Early clinical findings suggest that the use of such cells early or late after transplantation is associated with no acute toxicity, persistent circulation of the gene-modified cells (GMC) and GCV-sensitive GvHD. However, a number of limitations such as reduced immune function of gene-modified T-cells, immunogenicity of GMC as well as presence of a truncated HS-tk gene have emerged and need to be addressed.