NKG2D-ACE2 CAR-NK Cells are engineered natural killer (NK) cells made from chord blood. NK cells are part of the innate immune system that helps your body to kill virally-infected cells. These cells were then engineered to secrete an interleukin (IL)-15 superagonist (soluble IL-15 plus IL-15 receptor alpha chimeric protein; IL-15 is required for NK cell long-term survival in the body) and a single-chain variable fragment (scFv; a single-chain protein comprised of only the variable [specific] fragment of an antibody) that binds granulocyte-macrophage colony-stimulating factor (GM-CSF; a cytokine, that when neutralized, helps prevent a dangerous cytokine release syndrome associated with other cell therapies). Along with these secretable factors, these cells are chimeric antigen receptor (CAR) engineered to express the NKG2D membrane protein (an activating receptor of NK cells, which can recognize and thus clear virus-infected cells) and angiotensin-converting enzyme 2 (ACE2; the surface protein recognized by the SARS-CoV-2 spike protein) so that they can no only target and kill virally-infected cells, but also competitively inhibit SARS-CoV-2 infection of other cells through its ACE2 expression.
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