Author
Listed:
- Terese C. Hammond
(Pulmonary Critical Care Sleep Medicine, Providence Saint John’s Health Center
David Geffen School of Medicine at UCLA)
- 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
Agenus)
- Xin Song
(Agenus)
- Yu Qin
(MiNK Therapeutics
Agenus)
- Ilya Mishchenko
(Agenus)
- Maurice Kirby
(Agenus)
- Valeriia Nasonenko
(Agenus)
- Alexa Buffa
(MiNK Therapeutics
Agenus)
- Jennifer S. Buell
(MiNK Therapeutics)
- Dhan Chand
(Agenus)
- Marc Dijk
(MiNK Therapeutics)
- Justin Stebbing
(Anglia Ruskin University)
- Mark A. Exley
(Brigham & Women’s Hospital)
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.
Suggested Citation
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 &, 2024.
"A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome,"
Nature Communications, Nature, vol. 15(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-44905-z
DOI: 10.1038/s41467-024-44905-z
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