[PDF][PDF] Third‐party virus‐specific T cells eradicate adenoviraemia but trigger bystander graft‐versus‐host disease

W Qasim, S Derniame, K Gilmour, R Chiesa… - British journal of …, 2011 - academia.edu
W Qasim, S Derniame, K Gilmour, R Chiesa, M Weber, S Adams, K Rao, P Amrolia…
British journal of haematology, 2011academia.edu
The adoptive transfer of T cells with anti-viral properties against pathogens, such as
cytomegalovirus (CMV) and Epstein–Barr virus (EBV), from allogeneic donors to recipients
has been shown to be highly effective, both as prophylaxis and treatment for viral
reactivation following haematopoietic stem cell transplantation (HSCT)(Rooney et al, 1998;
Peggs et al, 2003; Leen et al, 2009). Conventional procedures for the generation of virus-
specific T cells require weeks of cell culture and most studies have therefore relied on the …
The adoptive transfer of T cells with anti-viral properties against pathogens, such as cytomegalovirus (CMV) and Epstein–Barr virus (EBV), from allogeneic donors to recipients has been shown to be highly effective, both as prophylaxis and treatment for viral reactivation following haematopoietic stem cell transplantation (HSCT)(Rooney et al, 1998; Peggs et al, 2003; Leen et al, 2009). Conventional procedures for the generation of virus-specific T cells require weeks of cell culture and most studies have therefore relied on the elective production and pre-emptive transfer of cells. Recently, tri-specific donor T cell populations with specificity against EBV, CMV and adenovirus (ADV) have been used in this manner (Leen et al, 2006). As an elective strategy this approach is highly effective, but is very labour intensive, time consuming and costly. An alternative approach, which allows rapid identification and enrichment of virus-specific donor cells, relies on the detection of gamma-interferon-(IFN-c) responses to pathogens following ex-vivo stimulation and offers more targeted therapy. A bi-specific antibody is used to ‘capture and fix’IFN-c as it is released from stimulated cells and magnetic bead selection bead is then used to isolate responding cells (Chatziandreou et al, 2006). The IFN-c capture strategy allows rapid selection of both CD4+ and CD8+ T cells and has recently been tested in pilot studies in the UK (Mackinnon et al, 2008) and Germany (Feuchtinger et al, 2006). We recently deployed this technology to identify and select virus-specific T cells from a third-party donor to treat intractable ADV viraemia following mis-matched unrelated donor stem cell transplantation. The patient, a 7-year-old girl who had suffered relapse of acute lymphoblastic leukaemia (ALL) 2 years after successful treatment with regimen A of the UK-ALL 2003 protocol, had undergone a 1C-mismatched unrelated donor peripheral blood HSCT. She received conditioning with total body irradiation (1440 cGy), cyclophosphamide (200 mg/kg) and alemtuzemab (1 mg/kg). Graft-versus-host disease (GVHD) prophylaxis had
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