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https://hdl.handle.net/2440/124443
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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 2473-9537 |
Statement of Responsibility: | 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 www.clinicaltrials.gov as #NCT02779439 and www.anzctr.org.au as #ACTRN12613000603718. |
Rights: | © 2017 by The American Society of Hematology |
DOI: | 10.1182/bloodadvances.2017010223 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1032431 |
Published version: | http://dx.doi.org/10.1182/bloodadvances.2017010223 |
Appears in Collections: | Aurora harvest 8 Medicine publications |
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