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Type: Journal article
Title: Long-term control of recurrent or refractory viral infections after allogeneic HSCT with third-party virus-specific T cells
Author: 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.
Citation: Blood Advances, 2017; 1(24):2193-2205
Publisher: American Society of Hematology
Issue Date: 2017
ISSN: 2473-9529
Statement of
Barbara Withers, Emily Blyth, Leighton E. Clancy, Agnes Yong, Chris Fraser, Jane Burgess ... et al.
Abstract: Donor-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 as #NCT02779439 and as #ACTRN12613000603718.
Rights: © 2017 by The American Society of Hematology
DOI: 10.1182/bloodadvances.2017010223
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