INKT (Invariant natural killer T cells) as a COVID-19 therapy

[Andrew Mason]

I would be interested in hearing from the experts such as @Ygggdrasil about the prospects for a new therapy for COVID-19 using iNKT cells. According to this information page from the British Society for Immunology site:

Invariant natural killer T (iNKT) cells, also known as type I or classical NKT cells, are a distinct population of T cells that express an invariant aβ T-cell receptor (TCR) and a number of cell surface molecules in common with natural killer (NK) cells. Although iNKT cells are rare in the human blood pool, comprising just 0.01-1% of peripheral blood mononuclear cells (PBMCs), they are important immunoregulatory cells rapidly producing large amounts of cytokines that can influence other immune cells.
...
Functionally, human iNKT cells can be divided into three subpopulations, which are either CD4+, CD8+ or CD4- CD8- (DN). In vitro studies have shown that CD4+ iNKT cells tend to produce both Th1 and Th2-type cytokines and may have a more immunoregulatory role, while CD8+ and DN iNKT cells appear more Th1-like in response and have a stronger cytolytic ability. iNKT cell-derived cytokines and chemokines can modulate several other cell types, including NK cells, conventional CD4+ and CD8+ T cells, macrophages, neutrophils and B cells as well as recruiting and activating dendritic cells.

My interest was piqued by a recent announcement by AgenusBio (Agenus Inc. and its subsidiary AgenTus Therapeutics) that "The FDA has cleared the IND for AGENT-797 for use in patients with COVID-19 and cancer. AgenTus is advancing iNKT cell therapy to the clinic for these diseases".

Apparently, iNKT therapy has been used very successfully on at least 4 severely ill COVID19 patients, three of whom responded very positively and quickly.

AM

 

[Greg Bernhardt]

I am right in thinking that Ygggdrasil is the best person to answer this question. If so, I would appreciate hearing more about their thoughts on the prospects of iNKT therapy for COVID-19.