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Multicenter phase 1/2 application of adenovirus-specific T cells in high-risk pediatric patients after allogeneic stem cell transplantation

Ip, W; Silva, JMF; Gaspar, H; Mitra, A; Patel, S; Rao, K; Chiesa, R; ... Qasim, W; + view all (2018) Multicenter phase 1/2 application of adenovirus-specific T cells in high-risk pediatric patients after allogeneic stem cell transplantation. Cytotherapy , 20 (6) pp. 830-838. 10.1016/j.jcyt.2018.03.040. Green open access

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Abstract

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.

Type: Article
Title: Multicenter phase 1/2 application of adenovirus-specific T cells in high-risk pediatric patients after allogeneic stem cell transplantation
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jcyt.2018.03.040
Publisher version: http://doi.org/10.1016/j.jcyt.2018.03.040
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: adenovirus-specific T cells, adoptive immunotherapy, hematopoietic stem cell transplantation
UCL classification: UCL
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 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/10054019
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