Scientists have created natural killer immune cells that not only kill tumor cells in the head and neck of mice, but also reduce the number of immunosuppressive myeloid cells that allow tumors to evade immune responses, a new study shows.
For patients whose immunotherapy based on activated T cells has failed, this engineered cell therapy could be used as an alternative to treating cancer. Researchers at the National Institutes of Health in Bethesda, Maryland, reported the findings.
In recent years, treatments called T-cell therapy or CAR-T cell therapy have been approved to treat blood cancers, and many other T-cell therapies are being developed to treat other cancers. However, these T-cell therapies rely on the ability to reprogram a patient’s own T-cells to express a chimeric antigen receptor (CAR) that strikes tumor cells. The process of reediting a patient’s own T cells is expensive and laborious.
High affinity natural killer cells mean that “untailored” cell therapies can be developed that do not rely on adapting a patient’s own immune cells. The same cells can be mass-produced and given to anyone. However, the presence of immunosuppressive myeloid cells in the tumor microenvironment still poses a barrier to immunotherapy including high affinity natural killer cell therapy.
To eliminate this barrier, researchers at the National Institute for Hearing Loss and Other Communication Disorders (NIDCD) and the National Cancer Institute, part of the NATIONAL Institutes of Health, used high-affinity natural killer cells that express a type of CAR to attack a molecule called programmed death ligand 1 (PD-L1). Pd-l1 is a molecule known to inhibit the immune system. Cancer cells and immunosuppressive myeloid cells produce large amounts of PD-L1.
Led by senior author Clint Allen, program leader of NIDCD’s Translational tumor Immunology division, the team tested the ability of engineered PD-L1 high-affinity natural killer cells and normal high-affinity natural killer cells to kill head and neck cancer cells in humans and mice. They found that high-affinity natural killer cells expressing PD-L1 CAR killed mouse and human tumor cells to a greater extent than high-affinity natural killer cells without CAR, and this ability was retained even after they had previously encountered pD-L1-carrying cells. This is important because natural killer cells are known to become “exhausted” after killing their target cells.