1,721,155 research outputs found
Twenty-five years of gene therapy for genetic diseases and leukemia: The road to marketing authorization of the first ex vivo gene therapies
No full textSuicide-gene transduced donor T cells for controlled graft-versus-host disease and graft-versus-tumor
No full textIn allogeneic hematopoietic cell transplantation, donor lymphocytes play a central therapeutic role in both graft-versus-leukemia and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GVHD). Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GVHD. Infusions of donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-tk) suicide gene resulted in anti-tumor activity in a substantial number of patients. Acute GVHD could be effectively controlled by ganciclovir-induced elimination of the transduced cells. Haplo-identical stem cell transplantation (haplo-SCT) is a promising therapeutic option for patients with high-risk hematologic malignancies lacking an HLA-matched donor. However, the intensive T-cell depletion required to overcome the risk of lethal GVHD has been associated with a delayed immune recovery with a prolonged risk of posttransplantation viral, fungal, and other opportunistic infections. Donor lymphocyte infusions of HSV-tk represent a promising tool for preventing disease relapse and promoting immune reconstitution after haplo-SCT, and a unique tool for the control of GVHD. The genetic manipulation of donor lymphocytes with a suicide gene is a promising strategy to increase feasibility and safety of allogeneic bone marrow transplantation
Suicide gene therapy for control of graft-versus-host disease
No full textIn allogeneic bone marrow transplantation, donor lymphocytes contribute to the development of GVHD, but can also confer protection,through graft versus leukemia, facilitating engraftment, and providing antiviral immunity. Here, Chiara Bonini and Claudio Bordignon summarize how a suicide gene in the delayed infusion of donor lymphocytes may help separate the two effects of donor lymphocytes
Effector-target cell interactions in vivo and in vitro in natural resistance to bone marrow grafts
No full textPotential of gene therapy in bone marrow transplantation
No full textGene therapy, initiated as a treatment for inherited disorders such as adenosine deaminase deficiency, is now a promising therapeutic strategy for malignancies and other acquired diseases. In particular, in the field of bone marrow transplantation (BMT) for haematological malignancies, the gene transfer of the suicide gene HSV-TK into donor lymphocytes allows control of the severe complication graft-versus-host disease (GVHD). The transfer of the HSV-TK suicide gene confers selective sensitivity to the drug ganciclovir, allowing in vivo elimination of the donor T-cells if severe GVHD occurs. In Italy, the first pilot study on delayed infusion of genetically engineered donor lymphocytes after T-depleted allogeneic BMT documented efficacy of engineered donor lymphocytes in terms of antitumour activity and efficiency of the suicide system. GVHD developed in 3 out of 8 patients and was successfully treated by ganciclovir administration
Suicide gene transduced for the regulation of the graft-versus-leukemia effect
No full textIn allogeneic marrow transplantation (BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia and immune reconstitution. However, their use is limited by the risk of severe graft-vs-host disease (GVHD). Different strategies have been investigated to obtain all the benefits derived from donor lymphocytes while avoiding the risk of GVHD. In the first pilot study, infusions of donor lymphocytes transduced with the Herpes Simplex virus thymidine kinase (HSV-tk) suicide resulted in anti-tumor activity in 50% of patients. Acute GVHD could be effectively controlled by ganciclovir-induced elimination of the transduced cells. If these results will be confirmed in larger studies, genetic manipulation of donor lymphocytes will increase efficacy and safety of allogeneic marrow transplantation
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