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

Conditional ablation of alloreactive donor T-cells to prevent or treat graf t-versus-host disease (GvHD) in the context of allogeneic haematopoietic st em cell transplantation could significantly contribute to expand the use of alloreactivity as a treatment modality, The prevention and treatment of Gv HD induced by herpes simplex virus 1-thymidine kinase (HS-tk)-expressing do nor T-cells by ganciclovir (GCV) has been demonstrated. Early clinical find ings suggest that the use of such cells early or late after transplantation is associated with no acute toxicity. persistent circulation of the gene-m odified cells (GMC) and GCV-sensitive GvHD. However, a number of limitation s 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.