A groundbreaking phase 1/2 clinical trial has demonstrated the potential of invariant natural killer T (iNKT) cell therapy in treating moderate-severe acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome-2 virus. The study, led by a team of esteemed researchers, has revealed promising results that could revolutionize the treatment of virally induced ARDS.
Published in Nature Communications, the open-label study focused on the use of agenT-797, a donor-unrestricted allogeneic ex vivo expanded iNKT cell therapy, in 21 ventilated patients, including 5 individuals receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO). The findings indicated that agenT-797 not only rescued exhausted T cells but also rapidly activated both innate and adaptive immunity, without any dose-limiting toxicities.
One of the most significant observations was the anti-inflammatory systemic cytokine response elicited by the infused iNKT cells, which remained persistent during follow-up, inducing only transient donor-specific antibodies. Moreover, the study revealed clinical signals of associated survival and prevention of secondary infections, pointing to the potential of cellular therapy using off-the-shelf iNKT cells as a safe and scalable approach with an anti-inflammatory response.
The safety and therapeutic potential of iNKT cells extend beyond ARDS, encompassing a wide range of diseases, including infections and cancer. As a result, the researchers have emphasized the need for randomized-controlled trials to further explore the therapeutic benefits of iNKT cells.
These groundbreaking findings shed light on the immense promise of iNKT cell therapy in addressing critical medical challenges, paving the way for further advancements in the field of cellular immunotherapy.
References:
1. Hammond, T. C. et al. A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome. Nature Communications 15, 974 (2024).
2. Exley, M. A. et al. Invariant natural killer T cell therapy: potential for infections and cancer. Nature Communications 15, 974 (2024).
