A Clinical Trial of a Gene Therapy to Regulate the Graft versus Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

In allogeneic hematopoietic transplantation, donor lymphocytes have important effects on both immunological reconstitution and graft versus leukemia effect. While we can treat leukemia relapsed after a stem cell transplantation by donor lymphocyte infusion (DLI), the indication of DLI is limited by the risk of graft versus host disease (GVHD). A clinical trial was started in the 1990s in Italy and was continued in Europe, which is a suicide gene therapy for a treatment of GVHD after DLI. Herpes simplex virus thymidine kinase (HSV-TK) was used as a suicide enzyme. A human cell does not have HSV-TK, and gancyclovir has no effect on it. Gancyclovir can be activated in the cell and expresses a cytotoxic effect after HSV-TK is transduced into a genome of a human cell. In our HSV-TK DLI project, we use HSV-TK transduced donor lymphocytes for DLI, and GVHD can be controled by gancyclovir-induced elimination of the transduced donor lymphocytes. In November of 2004, we carried out the HSV-TK DLI for the first case of our clinical protocol. It should be expanded to more patients for analysis of safety, efficacy and clinical contribution of this treatment.