Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells

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dc.contributor.authorWithers, B.
dc.contributor.authorBlyth, E.
dc.contributor.authorClancy, L.E.
dc.contributor.authorYong, A.
dc.contributor.authorFraser, C.
dc.contributor.authorBurgess, J.
dc.contributor.authorSimms, R.
dc.contributor.authorBrown, R.
dc.contributor.authorKliman, D.
dc.contributor.authorDubosq, M.-C.
dc.contributor.authorBishop, D.
dc.contributor.authorSutrave, G.
dc.contributor.authorMa, C.K.K.
dc.contributor.authorShaw, P.J.
dc.contributor.authorMicklethwaite, K.P.
dc.contributor.authorGottlieb, D.J.
dc.date.issued2017
dc.description.abstractDonor-derived adoptive T-cell therapy is a safe and effective treatment of viral infection posttransplant, but it is limited by donor serostatus and availability and by its personalized nature. Off-the-shelf, third-party virus-specific T cells (VSTs) appear promising, but the long-term safety and durability of responses have yet to be established. We conducted a prospective study of 30 allogeneic hemopoietic stem cell transplant (HSCT) patients with persistent or recurrent cytomegalovirus (CMV) (n = 28), Epstein-Barr virus (n = 1), or adenovirus (n = 1) after standard therapy. Patients were treated with infusions of partially HLA-matched, third-party, ex vivo-expanded VSTs (total = 50 infusions) at a median of 75 days post-HSCT (range, 37 to 349 days). Safety, viral dynamics, and immune recovery were monitored for 12 months. Infusions were safe and well tolerated. Acute graft versus host disease occurred in 2 patients, despite a median HLA match between VSTs and the recipient of 2 of 6 antigens. At 12 months, the cumulative incidence of overall response was 93%. Virological control was durable in the majority of patients; the reintroduction of antiviral therapy after the final infusion occurred in 5 patients. CMV-specific T-cell immunity rose significantly and coincided with a rise in CD8+ terminal effector cells. PD-1 expression was elevated on CD8+ lymphocytes before the administration of third-party T cells and remained elevated at the time of viral control. Third-party VSTs show prolonged benefit, with virological control achieved in association with the recovery of CD8+ effector T cells possibly facilitated by VST infusion. This trial was registered at www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718.
dc.description.statementofresponsibilityBarbara Withers, Emily Blyth, Leighton E. Clancy, Agnes Yong, Chris Fraser, Jane Burgess ... et al.
dc.identifier.citationBlood advances, 2017; 1(24):2193-2205
dc.identifier.doi10.1182/bloodadvances.2017010223
dc.identifier.issn2473-9529
dc.identifier.issn2473-9537
dc.identifier.orcidYong, A. [0000-0001-9452-1533]
dc.identifier.urihttp://hdl.handle.net/2440/124443
dc.language.isoen
dc.publisherAmerican Society of Hematology
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1032431
dc.rights© 2017 by The American Society of Hematology
dc.source.urihttps://doi.org/10.1182/bloodadvances.2017010223
dc.titleLong-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells
dc.typeJournal article
pubs.publication-statusPublished

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