Strategy for controlling graft-versus-host-disease (GVHD) by suicide gene therapy. The allogeneic donor serves as a source of lymphocytes that are genetically modified by introducing the suicide gene, which has the potential to convert a prodrug into an active drug. The vector genome includes a selectable marker gene that facilitates recovery of genetically modified cells. Following hematopoietic stem cell transplantation (HSCT), the recipient receives the genetically modified lymphocytes in an effort to accelerate restoration of lymphoid function. As shown on the right, this provides an opportunity for beneficial graft-versus-infection and graft-versus-leukemia affects. If GVHD occurs, administration of the prodrug results in ablation of allo-reactive lymphocytes and control of the disease. Reprinted from Bonini et al102 with permission.
