DONOR LYMPHOCYTES TRANSDUCED WITH HERPES SIMPLEX THYMIDINE KINASE GENE

点击翻译按钮获取中文摘要

This study will evaluate the safety and efficacy of allogeneic donor lymphocyte infusions in patients who have relapsed hematologic malignancies or Epstein Barr Virus Lymphoproliferative Syndrome (EBV-LPS) after allogeneic bone marrow transplantation (BMT). Donor lymphocyte transfusions have resulted in the cure of some patients with relapsed leukemia or lymphoproliferative disorder after allogeneic BMT, but has been complicated by the development of graft versus host disease (GvHD). We hypothesize that a retroviral vector containing the Herpes simplex thymidine kinase (HStk) gene will allow the anti-leukemia response of adoptive immunotherapy while allowing for selective destruction of these cells. Theoretically this should allow appreciation of graft versus leukemia (GvL) effect and termination of an unwanted degree GvHD. Patients with relapsed hematologic malignancies or EBV-LPS after allogeneic BMT will be infused with ex vivo gene modified donor lymphocytes. The HStk gene will be transduced into the cells ex vivo using PA317/LTKOSN.2 vector supernate. Insertion of the HStk gene into lymphocytes confers a sensitivity to the anti-herpes drug ganciclovir (GCV). This selective destruction of donor lymphocytes in situ will be used to abrogate the effects of graft versus host disease, if it develops.