Morris, EC;
Fox, T;
Chakraverty, R;
Tendeiro, R;
Snell, K;
Rivat, C;
Grace, S;
... Thrasher, AJ; + view all
(2017)
Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult.
Blood
, 130
pp. 1327-1335.
10.1182/blood-2017-04-777136.
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Abstract
Until recently hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harbouring integrations near oncogenes. Here, we describe a case of a pre-splenectomised 30 year old patient with severe WAS manifesting as cutaneous vasculitis, inflammatory arthropathy, intermittent polyclonal lymphoproliferation, significant chronic kidney disease and requiring long-term immunosuppressive treatment. Following reduced intensity conditioning there was rapid engraftment and expansion of a polyclonal pool of transgene-positive functional T cells, and sustained gene marking in myeloid and B cell lineages up to 20 months of observation. The patient was able to discontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculitic disease and pro-inflammatory markers. Autologous gene therapy using a lentiviral vector is a viable strategy for adult WAS patients with severe chronic disease complications and for whom an allogeneic procedure could present an unacceptable risk. This trial was registered at ClinicalTrials.gov #NCT01347242.
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