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A novel form of cell therapy may help patients who are critically ill with acute respiratory distress syndrome (ARDS) brought on by severe COVID-19, according to a study.
Professor Justin Stebbing of Anglia Ruskin University (ARU) is a co-senior author of a recent study that examines the application of agenT-797, an allogeneic, unmodified invariant natural killer T (iNKT) cell treatment developed by MiNK Therapeutics. The work was published in the journal Nature Communications. The iNKT cell therapy has the effect of rescuing depleted T cells and inducing an anti-inflammatory cytokine response, perhaps activating antiviral immunity to assist these patients fight infection while also reducing severe, pathogenic inflammation of the lung. The new research was carried out at three medical centres 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. 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 per cent) at 30 days (compared to a control group of 10 per cent), and there was an 80 per cent 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 per cent after 30 and 90 days, and 60 per cent after 120 days. This compares favourably to the overall survival of 51 per cent 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 favourable 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' 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 randomised 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." (ANI)
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