Ottaviano, G;
Chiesa, R;
Feuchtinger, T;
Vickers, MA;
Dickinson, A;
Gennery, AR;
Veys, P;
(2019)
Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation.
Cells
, 8
(1)
, Article 47. 10.3390/cells8010047.
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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.
| Type: | Article |
|---|---|
| Title: | Adoptive T Cell Therapy Strategies for Viral Infections in Patients Receiving Haematopoietic Stem Cell Transplantation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/cells8010047 |
| Publisher version: | https://doi.org/10.3390/cells8010047 |
| Language: | English |
| Additional information: | Haematopoietic stem cell transplantation; viral infections; adoptive cell therapy; third party donor |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, haematopoietic stem cell transplantation, viral infections, adoptive cell therapy, third party donor, EPSTEIN-BARR-VIRUS, ALLOGENEIC BONE-MARROW, LYMPHOPROLIFERATIVE DISORDERS, ADENOVIRUS INFECTION, CYTOMEGALOVIRUS-INFECTION, IMMUNE RECONSTITUTION, PEDIATRIC RECIPIENTS, CMV INFECTION, DONOR, IMMUNOTHERAPY |
| 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/10090424 |
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