137
Use of COX2 Knock Out Monocytes and Osteoclasts to Activate and Expand NK Cells
University of California - Los Angeles
Cell therapy
Oncology
Hit To Lead or Lead Optimization
• A monocyte and/or an osteoclast deficient in one or more biomarkers are effective in activating NK cells.
• Immunotherapy with NK cells has been limited due to inability to obtain sufficient numbers of highly functional NK cells, or an effective means to activate NK cells in vivo. Thus, there is a great need in the art to identify therapeutic compositions and methods for improved NK immunotherapy.
• The present invention is based, at least in part, on the discovery that a cancer vaccine comprising cancer cells deficient in one or more biomarkers are effective in activating NK cells and inducing immune response.
• Such deficiency results in de-differentiation of the cancer cells, and the proteins presented on their cell surface provide effective signals in activating various types of immune cells, including NK cells. Similarly, it has been determined herein that a monocyte and/or an osteoclast deficient in one or more biomarkers are effective in activating NK cells. The present invention provides compositions and methods to activate and expand large numbers of NK cells in vivo , in vitro , or ex vivo for use in immunotherapeutic strategies.
WO2022178138A1
• Adoptive transfer of osteoclast-expanded Natural Killer cells for immunotherapy targeting cancer stem-like cells in humanized mice. Cancer Immunol Immunother, (2016)
• Differential cytotoxicity but augmented IFN-γ secretion by NK cells after interaction with monocytes from humans, and those from wild type and myeloid-specific COX-2 knockout mice. Front Immunol, (2015)
