23 May 2022 - - Researchers at US-based cancer research and treatment organization City of Hope have engineered an immunotherapy using natural killer cells with a specific molecule that can target the SARS-CoV-2 virus' spike protein, providing a novel therapeutic pathway for the treatment of COVID-19 and other infections that include the spike protein, according to a study published in Nature Communications.

The research adds to city of Hope's leadership in using CAR T cell therapy, natural killer cells and other immunotherapies to help find better treatments against cancer and other diseases.

Natural killer cells are lymphocytes in the body that recognize and rapidly target abnormal cells, including cells infected with viruses.

Although NK cells are universal killers in the body's immune response against certain viruses or tumors, they lack specificity against SARS-CoV-2. Studies have revealed that COVID-19 patients have significantly decreased numbers of NK cells.

However, in this study, city of Hope researchers show that genetically modifying the NK cells with a chimeric antigen receptor or CAR that specifically "sees" the SARS-CoV-2 virus improves survival in animals infected with the virus.

The preclinical research study was led by Caligiuri and Jianhua Yu, Ph.D., city of Hope professor and director of the Natural Killer Cell Biology Research Program. Together, they have nearly 55 years of collective laboratory investigation of NK cells.

For the study, the team isolated NK cells from umbilical cord blood and used them to manufacture CAR-NK cells. These cells were then engineered to express ACE2 receptors, a protein that the virus sees and attaches to in order to enter a cell.

The CAR-NK cells use this ACE2 receptor to attach to the spike protein of SARS-CoV2, and then unleash their attack on the virus.

To prolong the survival of the NK cells, which typically have a short lifespan, the research team also engineered the CAR-NK cells to release IL-15, an immune hormone that can prolong NK cell survival in the body.

Next, the team administered the engineered NK cells to humanized mice infected with live SARS-CoV-2.

The results showed a reduced viral load and prolonged survival in the animal models. The team also tested the same cells after cryopreserving, or freezing, them and found that they retained their activity.

This finding, along with the global abundance of public umbilical cord blood banks for sourcing donor NK cells, would make the therapy more viable as an off-the-shelf therapy for COVID-19 patients.

Still, there is much work to be done to ensure that the treatment is safe, well-tolerated and effective in humans, although now over 30 patients have received genetically modified NK cells for the treatment of cancer without serious, life-threatening side effects, Caligiuri noted.

The research team hope to gain clearance to use their CAR-NK cell product in moderate to high-risk patients infected with SARS-CoV-2 in the near future.

City of Hope's mission is to deliver the cures of tomorrow to the people who need them TODAY.

Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the US and one of the leading research centers for diabetes and other life-threatening illnesses.

As an independent, National Cancer Institute-designated comprehensive cancer center, City of Hope brings an integrated model to patients, spanning cancer care, research and development, academics and training, and innovation initiatives.

City of Hope's affiliated family of organizations includes Translational Genomics Research Institute and AccessHope.