Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jan 14;8(1):47.
doi: 10.3390/cells8010047.

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

Affiliations
Review

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

Giorgio Ottaviano et al. Cells. .

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.

Keywords: adoptive cell therapy; haematopoietic stem cell transplantation; third party donor; viral infections.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Third-party CTL efficiently cleared viral load in a transplanted child with refractory AdV infection, although significant liver GvHD occurred afterwards. Adapted from Qasim et al. [61].

Similar articles

Cited by

References

    1. Hiwarkar P., Gaspar H.B., Gilmour K., Jagani M., Chiesa R., Bennett-Rees N., Breuer J., Rao K., Cale C., Goulden N., et al. Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients. Bone Marrow Transplant. 2013;48:803–808. doi: 10.1038/bmt.2012.221. - DOI - PubMed
    1. Lazzarotto T., Chiereghin A., Piralla A., Piccirilli G., Girello A., Campanini G., Gabrielli L., Costa C., Prete A., Bonifazi F., et al. Cytomegalovirus and Epstein-Barr virus DNA kinetics in whole blood and plasma of allogeneic hematopoietic stem cell transplantation recipients. Biol. Blood Marrow Transplant. 2018;24:1699–1706. doi: 10.1016/j.bbmt.2018.03.005. - DOI - PubMed
    1. Rustia E., Violago L., Jin Z., Foca M.D., Kahn J.M., Arnold S., Sosna J., Bhatia M., Kung A.L., George D., et al. Risk factors and utility of a risk-based algorithm for monitoring cytomegalovirus, Epstein-Barr virus, and adenovirus infections in pediatric recipients after allogeneic hematopoietic cell transplantation. Biol. Blood Marrow Transplant. 2016;22:1646–1653. doi: 10.1016/j.bbmt.2016.05.014. - DOI - PMC - PubMed
    1. Atay D., Akcay A., Erbey F., Ozturk G. The impact of alternative donor types on viral infections in pediatric hematopoietic stem cell transplantation. Pediatr. Transplant. 2018;22:e13109. doi: 10.1111/petr.13109. - DOI - PMC - PubMed
    1. Sedláček P., Petterson T., Robin M., Sivaprakasam P., Vainorius E., Brundage T., Chandak A., Mozaffari E., Nichols G., Voigt S. Incidence of adenovirus infection in hematopoietic stem cell transplant recipients: Findings from the AdVance study. Biol. Blood Marrow Transplant. 2018 doi: 10.1016/j.bbmt.2018.12.753. - DOI - PubMed