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Biomedicines 2017, 5(2), 30; doi:10.3390/biomedicines5020030

Exploiting Cell Death Pathways for Inducible Cell Elimination to Modulate Graft-versus-Host-Disease

Department of Medicine, Hematology-Oncology, Stem Cell Transplantation and Cellular Therapies, The University of Alabama at Birmingham, Birmingham, AL 35294, USA
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Received: 25 April 2017 / Revised: 5 June 2017 / Accepted: 8 June 2017 / Published: 14 June 2017
(This article belongs to the Special Issue Cell Therapy for the Treatment of GVHD)
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Abstract

Hematopoietic stem cell transplantation is a potent form of immunotherapy, potentially life-saving for many malignant hematologic diseases. However, donor lymphocytes infused with the graft while exerting a graft versus malignancy effect can also cause potentially fatal graft versus host disease (GVHD). Our group has previously validated the inducible caspase-9 suicide gene in the haploidentical stem cell transplant setting, which proved successful in reversing signs and symptoms of GVHD within hours, using a non-therapeutic dimerizing agent. Cellular death pathways such as apoptosis and necroptosis are important processes in maintaining healthy cellular homeostasis within the human body. Here, we review two of the most widely investigated cell death pathways active in T-cells (apoptosis and necroptosis), as well as the emerging strategies that can be exploited for the safety of T-cell therapies. Furthermore, such strategies could be exploited for the safety of other cellular therapeutics as well. View Full-Text
Keywords: cellular therapies; graft versus host disease (GVHD); inducible suicide genes; apoptosis; necroptosis cellular therapies; graft versus host disease (GVHD); inducible suicide genes; apoptosis; necroptosis
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Falcon, C.; AL-Obaidi, M.; Di Stasi, A. Exploiting Cell Death Pathways for Inducible Cell Elimination to Modulate Graft-versus-Host-Disease. Biomedicines 2017, 5, 30.

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