A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome

Terese C. Hammond, Marco A. Purbhoo, Sapana Kadel, Jerome Ritz, Sarah Nikiforow, Heather Daley, Kit Shaw, Koen 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 Dijk, Justin Stebbing () and Mark A. Exley
Additional contact information
Terese C. Hammond: Pulmonary Critical Care Sleep Medicine, Providence Saint John’s Health Center
Marco A. Purbhoo: MiNK Therapeutics
Sapana Kadel: MiNK Therapeutics
Jerome Ritz: Dana Farber Cancer Institute
Sarah Nikiforow: Dana Farber Cancer Institute
Heather Daley: Dana Farber Cancer Institute
Kit Shaw: Dana Farber Cancer Institute
Koen Besien: UH Seidman Cancer Center
Alexandra Gomez-Arteaga: Weill Cornell Medicine
Don Stevens: Norton Cancer Center
Waldo Ortuzar: Agenus
Xavier Michelet: MiNK Therapeutics
Rachel Smith: MiNK Therapeutics
Darrian Moskowitz: MiNK Therapeutics
Reed Masakayan: MiNK Therapeutics
Burcu Yigit: MiNK Therapeutics
Shannon Boi: MiNK Therapeutics
Kah Teong Soh: Agenus
John Chamberland: MiNK Therapeutics
Xin Song: Agenus
Yu Qin: MiNK Therapeutics
Ilya Mishchenko: Agenus
Maurice Kirby: Agenus
Valeriia Nasonenko: Agenus
Alexa Buffa: MiNK Therapeutics
Jennifer S. Buell: MiNK Therapeutics
Dhan Chand: Agenus
Marc Dijk: MiNK Therapeutics
Justin Stebbing: Anglia Ruskin University
Mark A. Exley: Brigham & Women’s Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-15

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.

Date: 2024
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DOI: 10.1038/s41467-024-44905-z

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