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Lookup NU author(s): Professor Mary Slatter,
Professor Andrew GenneryORCiD
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© 2018 Background: Adenovirus (ADV) reactivation can cause significant morbidity and mortality in children after allogeneic stem cell transplantation. Antiviral drugs can control viremia, but viral clearance requires recovery of cell-mediated immunity. Method: This study was an open-label phase 1/2 study to investigate the feasibility of generating donor-derived ADV-specific T cells (Cytovir ADV, Cell Medica) and to assess the safety of pre-emptive administration of ADV-specific T cells in high-risk pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT) to treat adenoviremia. Primary safety endpoints included graft-versus-host disease (GvHD), and secondary endpoints determined antiviral responses and use of antiviral drugs. Results: Between January 2013 and May 2016, 92 donors were enrolled for the production of ADV T cells at three centers in the United Kingdom (UK), and 83 products were generated from 72 mobilized peripheral blood harvests and 20 steady-state whole blood donations. Eight children received Cytovir ADV T cells after standard therapy and all resolved ADV viremia between 15 and 127 days later. ADV-specific T cells were detectable using enzyme-linked immunospot assay (ELISpot) in the peripheral blood of all patients analyzed. Serious adverse events included Grade II GvHD, Astrovirus encephalitis and pancreatitis. Conclusion: The study demonstrates the safety and feasibility of pre-emptively manufacturing peptide pulsed ADV-specific cells for high-risk pediatric patients after transplantation and provides early evidence of clinical efficacy.
Author(s): Ip W, Silva JMF, Gaspar H, Mitra A, Patel S, Rao K, Chiesa R, Amrolia P, Gilmour K, Ahsan G, Slatter M, Gennery AR, Wynn RF, Veys P, Qasim W
Publication type: Article
Publication status: Published
Print publication date: 01/06/2018
Online publication date: 09/05/2018
Acceptance date: 31/03/2018
ISSN (print): 1465-3249
ISSN (electronic): 1477-2566
Publisher: Elsevier BV
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