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Cells 2019, 8(1), 47; https://doi.org/10.3390/cells8010047

Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation

1
Department of Paediatrics, Milano-Bicocca University, Fondazione MBBM/San Gerardo Hospital, 20900 Monza, Italy
2
Blood & Marrow Transplant Unit, Great Ormond Street Hospital, UCL, London WC1N 3JH, UK
3
Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner University Children’s Hospital, LMU, 80337 Munich, Germany
4
Scottish National Blood Transfusion Service, Blood Transfusion Centre, Foresterhill Road, Aberdeen AB25 2ZW, UK
5
Infection, Immunity & Inflammation, Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK
6
Haematological Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
7
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
8
Paediatric HSCT Unit, Great North Children’s Hospital, Newcastle upon Tyne NE2 4HH, UK
9
Department of Applied Sciences, Faculty of Health & Life Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST 4HH, UK
*
Author to whom correspondence should be addressed.
Received: 20 December 2018 / Revised: 8 January 2019 / Accepted: 11 January 2019 / Published: 14 January 2019
(This article belongs to the Special Issue Emerging Cellular Therapies: T Cells and Beyond)
Full-Text   |   PDF [547 KB, uploaded 14 January 2019]   |  

Abstract

Adverse outcomes following virus-associated disease in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT) have encouraged strategies to control viral reactivation in immunosuppressed patients. However, despite timely treatment with antiviral medication, some viral infections remain refractory to treatment, which hampers outcomes after HSCT, and are responsible for a high proportion of transplant-related morbidity and mortality. Adoptive transfer of donor-derived lymphocytes aims to improve cellular immunity and to prevent or treat viral diseases after HSCT. Early reports described the feasibility of transferring nonspecific lymphocytes from donors, which led to the development of cell therapy approaches based on virus-specific T cells, allowing a targeted treatment of infections, while limiting adverse events such as graft versus host disease (GvHD). Both expansion and direct selection techniques have yielded comparable results in terms of efficacy (around 70–80%), but efficacy is difficult to predict for individual cases. Generating bespoke products for each donor–recipient pair can be expensive, and there remains the major obstacle of generating products from seronegative or poorly responsive donors. More recent studies have focused on the feasibility of collecting and infusing partially matched third-party virus-specific T cells, reporting response rates of 60–70%. Future development of this approach will involve the broadening of applicability to multiple viruses, the optimization and cost-control of manufacturing, larger multicentred efficacy trials, and finally the creation of cell banks that can provide prompt access to virus-specific cellular product. The aim of this review is to summarise present knowledge on adoptive T cell manufacturing, efficacy and potential future developments. View Full-Text
Keywords: haematopoietic stem cell transplantation; viral infections; adoptive cell therapy; third party donor haematopoietic stem cell transplantation; viral infections; adoptive cell therapy; third party donor
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MDPI and ACS Style

Ottaviano, G.; Chiesa, R.; Feuchtinger, T.; Vickers, M.A.; Dickinson, A.; Gennery, A.R.; Veys, P.; Todryk, S. Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation. Cells 2019, 8, 47.

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