Withers, B.Blyth, E.Clancy, L.E.Yong, A.Fraser, C.Burgess, J.Simms, R.Brown, R.Kliman, D.Dubosq, M.-C.Bishop, D.Sutrave, G.Ma, C.K.K.Shaw, P.J.Micklethwaite, K.P.Gottlieb, D.J.2020-04-292020-04-292017Blood advances, 2017; 1(24):2193-22052473-95292473-9537http://hdl.handle.net/2440/124443Donor-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.en© 2017 by The American Society of HematologyLong-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cellsJournal article003008701010.1182/bloodadvances.20170102230004151983000102-s2.0-85044154619392485Yong, A. [0000-0001-9452-1533]