Bibliographic Details
| 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] |
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| Database: |
Complementary Index |
