학술논문
A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome
Document Type
article
Author
Terese C. Hammond; Marco A. Purbhoo; Sapana Kadel; Jerome Ritz; Sarah Nikiforow; Heather Daley; Kit Shaw; Koen van Besien; Alexandra Gomez-Arteaga; Don Stevens; Waldo Ortuzar; Xavier Michelet; Rachel Smith; Darrian Moskowitz; Reed Masakayan; Burcu Yigit; Shannon Boi; Kah Teong Soh; John Chamberland; Xin Song; Yu Qin; Ilya Mishchenko; Maurice Kirby; Valeriia Nasonenko; Alexa Buffa; Jennifer S. Buell; Dhan Chand; Marc van Dijk; Justin Stebbing; Mark A. Exley
Source
Nature Communications, Vol 15, Iss 1, Pp 1-15 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
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.