A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome.
Document Type
Article
Publication Date
2-6-2024
Publication Title
Nat Commun
Keywords
Humans; Natural Killer T-Cells; Cytokines; Respiratory Distress Syndrome; Neoplasms; Anti-Inflammatory Agents; california; santa monica
Abstract
Invariant 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.
Clinical Institute
Cancer
Department
Oncology
Department
Sleep Medicine
Department
Critical Care Medicine
Recommended Citation
Hammond, Terese C; Purbhoo, Marco A; Kadel, Sapana; Ritz, Jerome; 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, Shannon; Soh, Kah Teong; Chamberland, John; Song, Xin; Qin, Yu; Mishchenko, Ilya; Kirby, Maurice; Nasonenko, Valeriia; Buffa, Alexa; Buell, Jennifer S; Chand, Dhan; van Dijk, Marc; Stebbing, Justin; and Exley, Mark A, "A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome." (2024). Articles, Abstracts, and Reports. 8526.
https://digitalcommons.providence.org/publications/8526
