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

Giorgio Ottaviano (Corresponding Author), Robert Chiesa, Tobias Feuchtinger, Mark A Vickers, Anne Dickinson, Andrew R Gennery, Paul Veys, Stephen Todryk

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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 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.

Original languageEnglish
Article number47
JournalCells
Volume8
Issue number1
DOIs
Publication statusPublished - 14 Jan 2019

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Hematopoietic Stem Cell Transplantation
Virus Diseases
Cell- and Tissue-Based Therapy
Viruses
T-Lymphocytes
Tissue Donors
Lymphocytes
Adoptive Transfer
Cost Control
Graft vs Host Disease
Cellular Immunity
Antiviral Agents
Therapeutics
Morbidity
Transplants
Mortality
Infection

Keywords

  • ADENOVIRUS INFECTION
  • ALLOGENEIC BONE-MARROW
  • CMV INFECTION
  • CYTOMEGALOVIRUS-INFECTION
  • DONOR
  • EPSTEIN-BARR-VIRUS
  • IMMUNE RECONSTITUTION
  • IMMUNOTHERAPY
  • LYMPHOPROLIFERATIVE DISORDERS
  • PEDIATRIC RECIPIENTS
  • adoptive cell therapy
  • haematopoietic stem cell transplantation
  • third party donor
  • viral infections

Cite this

Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation. / Ottaviano, Giorgio (Corresponding Author); Chiesa, Robert; Feuchtinger, Tobias; Vickers, Mark A; Dickinson, Anne; Gennery, Andrew R; Veys, Paul; Todryk, Stephen.

In: Cells, Vol. 8, No. 1, 47, 14.01.2019.

Research output: Contribution to journalReview article

Ottaviano, G, Chiesa, R, Feuchtinger, T, Vickers, MA, Dickinson, A, Gennery, AR, Veys, P & Todryk, S 2019, 'Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation' Cells, vol. 8, no. 1, 47. https://doi.org/10.3390/cells8010047
Ottaviano, Giorgio ; Chiesa, Robert ; Feuchtinger, Tobias ; Vickers, Mark A ; Dickinson, Anne ; Gennery, Andrew R ; Veys, Paul ; Todryk, Stephen. / Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation. In: Cells. 2019 ; Vol. 8, No. 1.
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AB - 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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