A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome
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Published:2024-02-06
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Hammond Terese C., Purbhoo Marco A., Kadel Sapana, Ritz JeromeORCID, Nikiforow Sarah, Daley Heather, Shaw Kit, van Besien Koen, Gomez-Arteaga Alexandra, Stevens Don, Ortuzar Waldo, Michelet Xavier, Smith Rachel, Moskowitz Darrian, Masakayan Reed, Yigit Burcu, Boi ShannonORCID, Soh Kah TeongORCID, Chamberland John, Song Xin, Qin Yu, Mishchenko Ilya, Kirby Maurice, Nasonenko Valeriia, Buffa AlexaORCID, Buell Jennifer S., Chand Dhan, van Dijk MarcORCID, Stebbing JustinORCID, Exley Mark A.ORCID
Abstract
AbstractInvariant natural killer T (iNKT) cells, a unique T cell population, lend themselves for use as adoptive therapy due to diverse roles in orchestrating immune responses. Originally developed for use in cancer, agenT-797 is a donor-unrestricted allogeneic ex vivo expanded iNKT cell therapy. We conducted an open-label study in virally induced acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome-2 virus (trial registration NCT04582201). Here we show that agenT-797 rescues exhausted T cells and rapidly activates both innate and adaptive immunity. In 21 ventilated patients including 5 individuals receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), there are no dose-limiting toxicities. We observe an anti-inflammatory systemic cytokine response and infused iNKT cells are persistent during follow-up, inducing only transient donor-specific antibodies. Clinical signals of associated survival and prevention of secondary infections are evident. Cellular therapy using off-the-shelf iNKT cells is safe, can be rapidly scaled and is associated with an anti-inflammatory response. The safety and therapeutic potential of iNKT cells across diseases including infections and cancer, warrants randomized-controlled trials.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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