小児幹細胞移植におけるＧＶＨＤ―未解決の課題と新しい展開　　遺伝子治療の応用―同種造血幹細胞移植におけるＧＶＨＤ制御への挑戦―

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

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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.

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