Immunotherapy for transplantation-associated viral infections
Claire Roddie, Karl S. Peggs
Claire Roddie, Karl S. Peggs
Published June 19, 2017
Citation Information: J Clin Invest. 2017;127(7):2513-2522. https://doi.org/10.1172/JCI90599.
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Review Series

Immunotherapy for transplantation-associated viral infections

Abstract

Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections following allogeneic hematopoietic stem cell transplantation (HSCT) are a major cause of morbidity and mortality. Early clinical trials demonstrate that adoptive transfer of donor-derived virus-specific T cells to restore virus-specific immunity is an effective strategy to control CMV and EBV infection after HSCT, conferring protection in 70%–90% of patients. The field has evolved rapidly to develop solutions to some of the manufacturing challenges identified in early clinical studies, such as prolonged in vitro culture, optimization of the purity of the virus-specific T cell product, the potential limitations of targeting a single viral antigen, and how to manage the patient with a virus-naive donor. This Review both discusses the seminal early studies and explores cutting-edge novel technologies that broaden the feasibility of and the scope for delivering virus-specific T cells to patients after HSCT.

Authors

Claire Roddie, Karl S. Peggs

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Figure 1

VST manufacture and direct selection methodology.

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VST manufacture and direct selection methodology. VSTs can be generated ...
VSTs can be generated by coculture of virus-derived peptides, proteins, or viral lysates with antigen-presenting cells (APCs) and T cells. However, these techniques are time-consuming and difficult to reproduce to good manufacturing practice (GMP) standards. Recently developed coculture methods include the use of gene-modified APCs that are engineered to present immunogenic viral peptides to T cells. This may allow for the generation of virus-reactive T cells from virus-naive donors. Direct selection techniques can permit rapid generation of VSTs to GMP standards and are now being used in clinical trials. Selection is delivered through IFN-γ capture or through multimer-based selection. LCL, lymphoblastoid cell lines; MoDC, monocyte-derived dendritic cell; LDA, limiting dilution assay.