Cancer

Cell culture and mouse studies suggest adoptive transfer of blood-derived, ex vivo-modified memory NK cells could help treat cancers. Memory NK cells derived from cytomegalovirus (CMV)-positive human donor blood and cultured for seven days with human IL-15 and a glycogen synthase kinase 3 (GSK3) inhibitor tool compound secreted higher levels of tumor necrosis factor α (TNFα) and interferon γ (IFNγ) than NK cells cultured without the GSK3 inhibitor. In human leukemia, lung cancer and pancreatic cancer cell lines, the GSK3 inhibitor-cultured NK cells plus Herceptin trastuzumab increased cell lysis and levels of antibody-dependent cellular cytotoxicity (ADCC) compared with NK cells cultured without the inhibitor plus an anti-CD20 control antibody. In a xenograft mouse model of ovarian cancer, the GSK3 inhibitor-cultured NK cells plus Herceptin decreased tumor growth compared with NK cells cultured without GSK3 inhibitor plus Herceptin. Ongoing work by Fate Therapeutics Inc. has included Phase I testing of Fate-NK100 cells, memory NK cells prepared using this method, to treat acute myelogenous leukemia (AML) and ovarian cancer (see "Fate's Killer Memory." BioCentury Innovations (Aug. 31, 2017)).

Fate has also submitted an IND for Fate-NK100 cells to treat hematologic malignancies and has the cells in preclinical testing to treat solid tumors...