iNKT Cells Safe, Shows Anti-Inflammatory Response in Patients With SARS-CoV-2
The cells may have potential to modulate disease in other cases of respiratory disease and critical illness.
Terese Hammond, MD
Invariant natural killer T (iNKT) cells were found to be safe and associated with an anti-inflammatory response in patients with virally induced acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2, according to findings from a phase 2 trial (NCT04582201).1
“When the pandemic began, we all felt pretty helpless. We had really no viable therapies to treat our patients. The ones that were getting intensely ill were requiring mechanical ventilation and even more sophisticated therapies like lung bypass and extracorporeal membrane oxygenation [ECMO] and were all dying at a pretty high rate. I think our survival rate initially was maybe 10 or 20%, when people got sick enough to be placed on mechanical support... I think all of us were searching for options and how to improve the outcomes in these tremendously ill patients,” first author Terese Hammond, MD, pulmonologist and medical director, cardiac care unit/intensive care unit, Saint John’s Health Center told CGTLive®.
Hammond and colleagues evaluated agent-797 in 21 patients on ventilation, including 5 participants receiving venovenous extracorporeal membrane oxygenation (VV-ECMO). Participants received 100 million (n = 3), 300 million (n = 4), or 109 iNKT cells (n = 14). The investigators observed no dose-limiting treatment-emergent adverse events (AEs) and no cytokine release syndrome. Most TEAEs were grade 1 or 2 and consistent with COVID-19/ARDS, including a grade 4 TRAE of dyspnea, anemia (n = 8), fever (n = 7), and acute kidney injury (n = 6).
“Allogeneic iNKT cells represent a novel approach for treating severe respiratory distress and these data underscore the important role that iNKT-based cell therapies could play in respiratory distress and critical illness more broadly,” Hammond said in a statement.2 “The results from this study support the notion that allogeneic, unmodified cell therapies can be administered to critically ill patients and may augment both innate and cell mediated immune responses, specifically viral pneumonia associated with COVID-19, and warrant further investigation.”
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Hammond and colleagues observed some signals of associated survival and secondary infection prevention. There was over an 80% numeric reduction of pneumonia in dose cohort 3 (15%) compared to cohorts 1 and 2 combined (71%). Out of 20 patients treated in the main trial, 14 (70%) survived. Out of the 5 participants on ventilation plus VV-ECMO, 4 (80%) survived at 30 days and 3 (60%) survived at 6 months.1
“Numbers are small and thus statistical analyses and conclusions are, in the context of this small non-placebo controlled clinical trial… naturally exploratory in nature,” Hammond and colleagues wrote.1
"These published results emphasize the distinctive qualities of iNKT cells and their pivotal role in modulating immunity. What is particularly exciting are the observations of disease modifying properties of iNKTs in immune related diseases such as ARDS and cancer, all in the context of a tolerable safety profile not observed with other cell therapy approaches. AgenT-797 offers a versatile approach to treating various illnesses and MiNK has developed the manufacturing platform to deliver this therapy at scale for patients facing life-threatening diseases,” Marc van Dijk, PhD, Chief Scientific Officer, MiNK, added to the statement.2 “The company plans to further advance agenT-797 in patients with viral ARDS through an externally funded, large platform trial.”
