The Health Pioneer shares details of a novel cell therapy that has emerged as a beacon of hope for patients grappling with Acute Respiratory Distress Syndrome (ARDS), a severe and often life-threatening condition characterized by widespread inflammation in the lungs
This groundbreaking therapy, heralded as a potential game-changer in critical care medicine, represents a significant stride forward in the ongoing battle against respiratory ailments. Published in the journal Nature Communications, Professor Justin Stebbing of Anglia Ruskin University (ARU), a joint senior author of the new study investigating the use of agenT-797, MiNK Therapeutic allogeneic, unmodified invariant natural killer T (iNKT) cell therapy.
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 centres at Weill Cornell Medicine, New York; The Norton Cancer Center, Louisville; and Providence Saint John’s Health Center, Santa Monica. It 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 present exploratory trial we are discussing here 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 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’ 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 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.”
“This pioneering approach holds the potential to revolutionize the treatment paradigm for ARDS and pave the way for transformative breakthroughs in critical care medicine,” noted the study.
ARDS and kids
Most often in children, it is caused by pneumonia, sepsis and aspiration. It is associated with significant morbidity related to secondary infection, prolonged hospital admission, critical illness neuropathy and a reduction in health related QOL.
A study has said, childhood survivors of ARDS have a 30% chance of being readmitted to the hospital within one year, with 50% of those readmissions likely to occur within 61 days of being discharged. Receiving a procedure that opens the windpipe known as a tracheostomy and staying in the hospital longer than two weeks also played a role. The study is published in JAMA Network Open. A deeper analysis excluding the kids with chronic conditions, still showed a longer length of stay was associated with readmission.
Causes, Symptoms, stages, EXTENT
ARDS is a life-threatening lung injury which can also be caused by sepsis, pneumonia and other conditions besides Covid-19. Sepsis is the most common cause of ARDS. It can happen when you have a serious infection in your lungs (pneumonia) or other organs with widespread inflammation. Aspiration pneumonia: Aspiration of stomach contents into your lungs may cause severe lung damage and ARDS. Aspiration is when food, liquid or other substances get into your airway and lungs. Blood transfusions: You’re at risk for ARDS if you receive more than 15 units of blood in a short period of time. COVID-19: The COVID-19 virus may develop into severe ARDS. Pancreatitis: Severe inflammation in your pancreas. Major trauma or burns: Accidents and falls may directly damage your lungs or other organs in your body and trigger severe inflammation in your lungs. Inhalational injury: Breathing and exposure to high concentrations of chemical fumes or smoke. Drug overdose: An overdose on drugs like cocaine and opioids. Drowning or near drowning: Drowning causes water to get into your lungs, causing damage.
lHealthcare providers sometimes classify ARDS into three stages: exudative, proliferative and fibrotic. This classification mainly describes the level of inflammation and fluid buildup, and the subsequent repair process that your lungs go through to heal. Not all people progress to the third stage, which mainly describes the formation of scar tissue in your lungs and a prolonged need for ventilation.
lARDS affects about 3 million people worldwide every year. ARDS causes around 10 per cent of all intensive care unit (ICU) admissions. It’s the reason at least 25 per cent of people require mechanical ventilation in a hospital setting.
lThose who are already in the hospital due to an injury or illness are most at risk for ARDS. But, just because you’re hospitalized, doesn’t mean you’ll end up in respiratory distress. Some factors that can increase your risk include being older than 65, tobacco use, substance abuse disorder and having lung disease. It tends to develop within a few hours to a few days of the event that caused it, and can worsen quickly. People with ARDS may have to be put in an intensive care unit (ICU) and on a ventilator to help them breathe. ARDS prevents other organs such as your brain, heart, kidneys and stomach from getting the oxygen they need to function.
A study has suggested that patients with ARDS and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in hospital than patients with ARDS without PH.