Costimulation Blockade in Vascularized Composite Allotransplantation.
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2020-01
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Vascular composite allotransplantation (VCA) is a field under research and has emerged as an alternative option for the repair of severe disfiguring defects that result from infections or traumatic amputation in a selected group of patients. VCA is performed in centers with appropriate expertise, experience and adequate resources to effectively manage the complexity and complications of this treatment. Lifelong immunosuppressive therapy, immunosuppression associated complications, and the effects of the host immune response in the graft are major concerns in VCA. VCA is considered a quality of life transplant and the risk-benefit ratio is dissimilar to life saving transplants. Belatacept seems a promising drug that prolongs patient and graft survival in kidney transplantation and it could also be an alternative approach to VCA immunosuppression. In this review, we are summarizing current literature about the role of costimulation blockade, with a focus on belatacept in VCA.
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Giannis, Dimitrios, Dimitrios Moris and Linda C Cendales (2020). Costimulation Blockade in Vascularized Composite Allotransplantation. Frontiers in immunology, 11. p. 544186. 10.3389/fimmu.2020.544186 Retrieved from https://hdl.handle.net/10161/27253.
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Linda Carime Cendales
Vascularized composite allotransplantation (VCA) refers to the transplantation of multiple tissues, such as skin, muscle, tendon, nerve, and/or bone, as a functional unit (e.g. a hand, an abdominal wall). Several recent advances in clinical organ transplant immunosuppression and experimental VCA have now made it feasible to consider clinical VCA for functional restoration in patients with the loss of one or both hands or large tissue defects that may not be reconstructed with autologous tissue. My research facilitates the translation of VCA from the bench to the bedside.
Our group has established preclinical models to understand VCA rejection in different tissues and to use that insight to minimize immunosuppression in VCA recipients who participate in clinical trials. We also organized the first public international consensus discussions conference in VCA at the Ninth Banff Conference on Allograft Pathology in Spain in 2007 resulting in the Banff VCA 2007 classification for skin allograft pathology. Additionally, we established a VCA Consortium to enable the comprehensive analysis of samples from patients in VCA clinical trials around the country.
Based on our studies of different immunosuppressive regimens in primates, we have been the first to show that belatacept prevents rejection in VCA in primates and controls rejection in humans. We are currently investigating this approach in a clinical trial of hand transplant recipients (NCT02310867). This clinical trial aims to determine the safety and efficacy of hand transplantation as a treatment for patients with limb loss. This study will also test the efficacy of belatacept to prevent rejection of the transplanted hand. We are also currently investigating in a clinical trial the efficacy of abdominal wall transplantation for the reconstruction of abdominal wall defects (NCT03310905).
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