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Paediatric immune reconstitution with adenovirus adoptive immunotherapy post haematopoietic stem cell transplant

Ip, WYW; (2016) Paediatric immune reconstitution with adenovirus adoptive immunotherapy post haematopoietic stem cell transplant. Doctoral thesis , UCL (University College London). Green open access

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Paediatric Immune Reconstitution with Adenovirus Adoptive Immunotherapy post Haematopoietic Stem Cell Transplant - with corrections.pdf - Accepted version

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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).

Type: Thesis (Doctoral)
Title: Paediatric immune reconstitution with adenovirus adoptive immunotherapy post haematopoietic stem cell transplant
Event: University College of London
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1478232
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