A new study suggests that modified natural killer cells, which express a chimeric antigen receptor using antibody, can bind to and inactivate SARS-CoV-2 spike protein in vitro. The global scientific community’s effort to combat the severe acute respiratory syndrome coronavirus, which causes coronavirus disease, includes vaccines, convalescent plasma, monoclonal antibody cocktails, and other repurposed drugs. Although some vaccines have already been approved for public use, their long-term effects are not yet known. Their efficacy against new and emerging variants of the virus is unknown, and some patients may even be unresponsive to the vaccines. Thus, there is a need for other strategies to combat the virus.

Natural killer (NK) cells are found in cord blood, peripheral blood, bone marrow, and embryonic stem cells, which can be isolated and modified to express a chimeric antigen receptor for treating infectious diseases. Compared to CAR-T cells, CAR-NK cells have lower host cytotoxicity and are less likely to induce the cytokine release syndrome that is associated with severe COVID-19. NK cells are involved in fighting viral infections and, as innate immune response cells, can quickly respond to and target viral infections. The half-life of monoclonal antibody therapies is about 21 days. However, using NK cells can likely protect for longer by increasing their persistence. Thus, modified NK cells could be a potent therapy for COVID-19. The team found that NK cells bind to pseudotyped nk cells with a lower binding efficiency than that to recombinant spike protein. However, they bind more strongly to the virus than to cells expressing the human angiotensin-converting enzyme.

CR3022-CAR-NK is another natural killer cells generated from the neutralizing antibody, which binds only to the open configuration of the spike protein trimer. Testing this and NK on cells expressing and spike protein showed NK had lower killing ability, suggesting conformation of the spike protein trimer is important in  recognition and binding. Thus, the data indicate NK could be a potential therapeutic strategy to combat COVID-19.

The use of the potent neutralizing antibody indicates this new approach could work against new mutations of the virus that are quickly spreading worldwide. The use of NK cells lines, which can be manufactured easily, and NK cells from expanded human blood for producing CAR-NK allows producing enough quantities of CAR-NK cells.

Media Contact
David Paul
Managing Editor
Journal of Infectious Diseases and Diagnosis