How Natural Killer Cell Therapy Offers a Lifeline to COVID-19 ARDS Patients

Recent trials of the iNKT cell therapy agenT-797 have demonstrated significant improvements in survival rates for critically ill COVID-19 patients with ARDS. This innovative treatment, which bolsters the immune response and reduces inflammation, offers hope for broader applications beyond COVID-19. Credit: SciTechDaily.com

Initial trial suggests invariant natural killer cell therapy improves survival.

Promising trial results indicate that a new type of cell therapy could improve the prognosis of those who are critically ill with acute respiratory distress syndrome (ARDS) resulting from severe COVID-19.

Published in the journal Nature Communications, Professor Justin Stebbing of Anglia Ruskin University (ARU) is the joint senior author of the new study investigating the use of agenT-797, MiNK Therapeutic’s allogeneic, unmodified invariant natural killer T (iNKT) cell therapy.

iNKT Cell Therapy: A Ray of Hope

The iNKT cell therapy has the effect of rescuing exhausted T cells and prompting an anti-inflammatory cytokine response, potentially activating anti-viral immunity to help these patients fight infection as well as to reduce severe, pathogenic inflammation of the lung.

The new research was carried out at three medical centers and found that agenT-797, which is also under investigation in cancer trials, could be manufactured rapidly, had a tolerable safety profile, and appeared to have a positive effect on mortality among critically unwell COVID-19 ARDS patients receiving intensive care.

Trial Results and Future Prospects

The exploratory trial included 20 mechanically ventilated patients with severe ARDS secondary to COVID-19. Of the 20 patients in the trial, 14 survived (70%) at 30 days (compared to a control group of 10%), and there was an 80% lower occurrence of bacterial pneumonia amongst those who received the highest dosage of agenT-797, compared to those who received fewer cells.

Twenty-one patients were treated overall (the main trial, plus one under compassionate use), which included five who were also receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO), known as ‘the most aggressive salvage therapy’ for critically ill patients with ARDS. In VV-ECMO, deoxygenated blood is pumped through a membrane lung and returned to the body via a cannula.

This trial is believed to be the first immune cell therapy of any type to be used in critically unwell patients undergoing VV-ECMO. Survival of the VV-ECMO cohort was 80% after 30 and 90 days, and 60% after 120 days. This compares favorably to overall survival of 51% for patients with COVID-19 who were treated with just VV-ECMO at the same institution, during the same timeframe.

Joint senior author Justin Stebbing, Professor of Biomedical Sciences at Anglia Ruskin University (ARU) in Cambridge, England, said: “During this small, exploratory study we observed that MiNK’s iNKT cell treatment, which is also being advanced for people with cancer, triggered an anti-inflammatory response in ARDS patients.

“Despite a poor prognosis, critically ill patients treated with this therapy showed favorable mortality rates and those treated at the highest dose also had reduced rates of pneumonia, underscoring the potential application of iNKT cells, and agenT-797 in particular, in treating viral diseases and infections more broadly.

“AgenT-797 was manufactured rapidly and as opposed to using patients’ own cells, it is ‘off-the-shelf’ and made from healthy donors’ cells. The potential of this therapy to be used across a number of severe infections warrants randomized controlled trials.”

Dr. Marc van Dijk, Chief Scientific Officer at MiNK and co-author of the study, said: “These published findings reinforce the unique power and potential of iNKT cells to mitigate severe acute respiratory distress.

“The data demonstrate agenT-797’s encouraging survival benefit, ability to help clear secondary infections, and tolerable administration in ventilated patients and those on VV-ECMO support.”

The study is published in the journal Nature Communications.

Reference: “A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome” by Terese C. Hammond, Marco A. Purbhoo, Sapana Kadel, Jerome Ritz, Sarah Nikiforow, Heather Daley, Kit Shaw, Koen van 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 van Dijk, Justin Stebbing and Mark A. Exley, 6 February 2024, Nature Communications.
DOI: 10.1038/s41467-024-44905-z

The trial was funded by MiNK Therapeutics, and patients were treated at Weill Cornell Medicine, New York; The Norton Cancer Center, Louisville; and Providence Saint John’s Health Center, Santa Monica.