First T-Cell Therapy Improves Survival in ARDS Patients

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.

Justin Stebbing, MBBS, FRCP, FRCPath, PhD, MD, professor at Anglia Ruskin University (ARU) is the joint senior author of the new study investigating the use of agenT-797, an allogeneic, unmodified invariant natural killer T (iNKT)-cell therapy, published in Nature Communications.

The iNKT-cell therapy has the effect of rescuing exhausted T cells and prompting an anti-inflammatory cytokine response, potentially activating antiviral 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 had a positive effect on mortality among critically unwell COVID-19 ARDS patients receiving intensive care.

Effect of agenT-797 cell therapy on ARDS patients

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

Some 21 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), 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 percent after 30 and 90 days, and 60 percent after 120 days. This compares favorably to the overall survival of 51 percent for patients with COVID-19 who were treated with just VV-ECMO at the same institution, during the same timeframe.

Stebbing 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.”

- This press release was originally published on the Anglia Ruskin University website