UCLA researchers in the Department of Dentistry have developed a novel combination immunotherapy using multiple immune cell types including NK and CD8+ T cells for the effective treatment of cancer.
Lymphocytes, a type of white blood cell used to fight infection, encompass a population of T-cells, B-cells, and the natural-killer cells (NK cells). NK cells defend against viral infection and have the potential to lyse and differentiate cancer stem cells, to prevent tumor growth. The cytotoxic CD8+ T cells are associated with the chemo-response against cancer by providing adaptive immunity to work in tandem with NK cells. In patients with advanced stage cancers, both NK and T cells have significantly reduced function with a specific decrease in cytotoxic activity. Although immunotherapy with a single type of immune cells has been moderately effective in the treatment of tumors, complete eradication of tumors using single cell type therapy has never been demonstrated. Consequently, there is a need to develop immunotherapies comprised of multiple immune cell types, to efficiently target cancer cells using several mechanisms.
UCLA researchers have discovered that combination treatment of primary NK cells, super-charged NK cells, and osteoclast expanded CD8+ cells elicits an expanded immune response to cancers. This treatment is particularly effective because it provides multiple cells that are defective in cancer patients. Primary NK cells facilitate antibody-dependent cellular cytotoxicity (ADCC) against differentiated tumors but not cancer stem cells/undifferentiated tumors, while super-charged NK cells do not mediate ADCC but are able to effectively target differentiated tumors. Further, CD8+ cells are preferentially expanded by NK cells to provide increased cytotoxic effects. This treatment prevents tumor growth and induces remodeling of the tumor microenvironment such that tumors have decreased metastatic potential, aggressiveness, and increased vulnerability to chemotherapy or alternative treatments.
This invention has been successfully tested in human tumor cell lines and tumor-bearing humanized mouse models.
cancer, CD8+ cells, NK cells, K cells, IL-2, undifferentiated tumors, pancreatic cancer, tumors, osteoclast expanded CD8+ T cells, osteoclast, oral cancer, cancer stem cells, immunotherapy