Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly contagious presenting a significant public health issue. Current therapies used to treat
coronavirus disease 2019 MESHD (
COVID-19 MESHD) include monoclonal antibody cocktail, convalescent plasma, antivirals, immunomodulators, and anticoagulants, though the current therapeutic options remain limited and expensive. The vaccines from Pfizer and Moderna have recently been authorized for emergency use, which are invaluable for the prevention of
SARS-CoV-2 infection MESHD. However, their long-term side effects are not yet to be documented, and populations with immunocompromised conditions (e.g., organ-transplantation and
immunodeficient MESHD patients) may not be able to mount an effective immune response. In addition, there are concerns that wide-scale immunity to SARS-CoV-2 may introduce immune pressure that could select for escape mutants to the existing vaccines and monoclonal antibody therapies. Emerging evidence has shown that chimeric antigen receptor (
CAR HGNC)- natural killer (NK) immunotherapy has potent antitumor response in
hematologic cancers MESHD with minimal adverse effects in recent studies, however, the potentials of
CAR HGNC-NK cells in preventing and treating severe cases of
COVID-19 MESHD has not yet been fully exploited. Here, we improve upon a novel approach for the generation of
CAR HGNC-NK cells for targeting SARS-CoV-2 and its D614G mutant.
CAR HGNC-NK cells were generated using the scFv domain of S309 (henceforward, S309-
CAR HGNC-NK), a
SARS-CoV and SARS-CoV-2 MESHD neutralizing antibody that targets the highly conserved region of
SARS-CoV-2 spike MESHD SARS-CoV-2 spike PROTEIN (
S) glycoprotein PROTEIN, therefore would be more likely to recognize different variants of SARS-CoV-2 isolates. S309-
CAR HGNC-NK cells can specifically bind to pseudotyped SARS-CoV-2 virus and its D614G mutant. Furthermore, S309-
CAR HGNC-NK cells can specifically kill target cells expressing SARS-CoV-2
S protein PROTEIN in vitro and show superior killing activity and cytokine production, compared to that of the recently published CR3022-
CAR HGNC-NK cells. Thus, these results pave the way for generating off-the-shelf S309-
CAR HGNC-NK cells for treatment in high-risk individuals as well as provide an alternative strategy for patients unresponsive to current vaccines.