DONOR LYMPHOCYTES TRANSDUCED WITH HERPES SIMPLEX THYMIDINE KINASE GENE

本研究将评估异基因供者淋巴细胞输注在异基因骨髓移植(BMT)后复发的恶性血液病或EB病毒淋巴增殖性综合征(EBV-LPS)患者中的安全性和有效性。供者淋巴细胞输注已经治愈了一些异基因骨髓移植后复发的白血病或淋巴增生性疾病，但由于移植物抗宿主病(GvHD)的发展而变得复杂。我们假设，含有单纯疱疹病毒胸苷激酶(HStk)基因的逆转录病毒载体将允许过继免疫治疗的抗白血病反应，同时允许选择性地破坏这些细胞。从理论上讲，这应该可以评估移植物抗白血病(GVL)的效果，并终止不想要的程度的GvHD。复发的恶性血液病患者或异基因骨髓移植后EBV-LPS患者将接受体外基因修饰的供者淋巴细胞输注。用PA317/LTKOSN.2载体上清将HStk基因导入细胞。将HStk基因插入淋巴细胞使其对抗疱疹药物更昔洛韦(GCV)具有敏感性。这种对供者淋巴细胞的选择性原位破坏将用于消除移植物抗宿主病的影响，如果它发展起来的话。

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.