| Title: |
A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome. |
| Authors: |
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 |
| Source: |
Nature Communications; 2/6/2024, Vol. 15 Issue 1, p1-15, 15p |
| Subject Terms: |
ADULT respiratory distress syndrome, CYTOTOXIC T cells, KILLER cells, T cells, T cell receptors, CELLULAR therapy, CLINICAL trials, EXTRACORPOREAL membrane oxygenation |
| 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. Invariant natural killer T (iNKT) cells recognize abnormal cells, but their T cell receptor is not variable and kill cancerous or infected target cells without MHC I restriction. Here, the authors show that in a clinical trial, donor-unrestricted allogeneic iNKT cells could be safely administered to human COVID-19 patients suffering from acute respiratory distress syndrome and trigger an anti-inflammatory response. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature Communications is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
