Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.790230
Title: Paediatric immune reconstitution with adenovirus adoptive immunotherapy post haematopoietic stem cell transplant
Author: Ip, W. Y. W.
ISNI:       0000 0004 8503 7725
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Abstract:
Adenovirus (ADV) can cause significant morbidity and mortality in children following allogeneic haemtopoietic stem cell transplantation (HSCT) when immunity is compromised. HSCT can offer a cure for many haematological diseases, primary immunodeficiencies, and inborn errors of metabolism. However not all transplant recipients have fully matched sibling donors and alternative donor sources have to be sought. In HLA-matched or mismatched unrelated donor setting, conditioning regimens will often include serotherapy such as Alemtuzumab (monoclonal anti-CD52 antibody) or thymoglobulin (polyclonal rabbit thymocyte globulin [ATG]) to remove donor alloreactive T cells that can cause acute Graft versus Host Disease (GVHD). During the post-transplant period of reduced T-cell immunity when reconstitution of donor-derived immune system is slow and the use of immunosuppressive agents is necessary, transplant recipients are vulnerable to viral reactivations and/or infections with CMV, EBV, or ADV (Hiwarkar et al., 2012) and other viruses. Whilst antivirals such as Ribavirin and Cidofovir are available for the treatment of ADV, they are associated with toxicity and have variable efficacy. It has been demonstrated that reconstitution of virus-specific immunity is essential to control viral infection after allo-HSCT (Feuchtinger et al., 2005a; Heemskerk et al., 2005). Over the past 2 decades, adoptive transfer of donor-derived virus specific T cells has been explored extensively as an alternative method to prevent and treat ADV and other viral infections post-HSCT. This thesis examines recent pre-clinical and clinical studies on T-cell Immunotherapy for ADV and presents data from a phase1/2 first-in-man trial of using donor-derived ADV CTLs in high-risk paediatric HSCT patients (ASPIRE trial).
Supervisor: Qasim, W. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.790230  DOI: Not available
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