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

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    Author(s)
    Ottaviano, Giorgio
    Chiesa, Robert
    Feuchtinger, Tobias
    Vickers, Mark A
    Dickinson, Anne
    Gennery, Andrew R
    Veys, Paul
    Todryk, Stephen
    Griffith University Author(s)
    Todryk, Stephen M.
    Year published
    2019
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    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 ...
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    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.
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    Journal Title
    Cells
    Volume
    8
    Issue
    1
    DOI
    https://doi.org/10.3390/cells8010047
    Copyright Statement
    © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
    Subject
    Medical and Health Sciences
    Science & Technology
    Life Sciences & Biomedicine
    Cell Biology
    haematopoietic stem cell transplantation
    viral infections
    Publication URI
    http://hdl.handle.net/10072/386821
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