Fate Therapeutics Announces Publication of FT538 Preclinical Data Demonstrating Enhanced Serial Killing and Functional Persistence without Cytokine Support
September 15, 2021 at 08:00 AM EDT
SAN DIEGO, Sept. 15, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, announced today the publication of preclinical data demonstrating that its off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate FT538 exhibits significantly enhanced serial killing and functional persistence compared to peripheral blood NK cells. The superior anti-tumor activity of FT538 was attributable to its novel engineered components, including the knockout of CD38 and the expression of IL-15/IL-15R fusion protein, which were shown to improve metabolic fitness, increase resistance to oxidative stress, and induce transcription of proteins that control NK cell activation and effector function. The data were published in Cell Stem Cell in an online article entitled “Harnessing features of adaptive NK cells to generate iPSC-derived NK cells for enhanced immunotherapy”.
“The NK cell community has long sought to improve NK cell activation, cytotoxicity, functional persistence, and tumor targeting for cancer immunotherapy. Our preclinical data demonstrate that the synthetic features of FT538 uniquely harness all these therapeutic attributes and significantly improve NK cell anti-tumor activity,” said Bob Valamehr, Ph.D., Chief Research and Development Officer of Fate Therapeutics. “We are excited to bring FT538 to patients for off-the-shelf treatment of hematologic malignancies and solid tumors, and to continue to leverage its multiplexed engineered backbone as the foundation for development of multi-antigen, CAR-targeted product candidates.”
The studies in the Cell Stem Cell publication were conducted as part of a collaboration between scientists at Fate Therapeutics and the laboratory of Jeffrey S. Miller, M.D., University of Minnesota, and were led by Frank Cichocki, Ph.D., University of Minnesota. The Miller laboratory has previously shown that a rare subset of NK cells with memory-like properties that arise in response to cytomegalovirus, known as adaptive NK cells, have a genome-wide epigenetic profile and recall response that parallel cytotoxic effector CD8+ T cells. These adaptive NK cells persist long term, exhibit a unique metabolic profile with elevated mitochondrial oxidative phosphorylation and glycolysis as well as increased levels of ATP, and have enhanced cytotoxicity.
The peer-reviewed paper describes preclinical studies showing that FT538 shares metabolic, transcriptional, and functional features with adaptive NK cells. The data demonstrate that FT538 persists in vivo at high levels for more than six weeks in the absence of cytokine support after adoptive transfer, whereas adoptively-transferred peripheral blood NK cells required the co-infusion of either IL-2 or IL-15 to achieve low-level persistence for up to two weeks. Additionally, in sequential killing assays, FT538 was shown to have robust serial killing and functional persistence, which were not observed with peripheral blood NK cells. FT538 also incorporates a novel high-affinity, non-cleavable CD16 Fc receptor as a third functional component, which was shown to mediate potent in vivo anti-tumor activity in combination with the CD38-targeted monoclonal antibody daratumumab against MM.1S myeloma cells.
FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia and in combination with daratumumab for the treatment of multiple myeloma (NCT04614636). In addition, the Company has initiated patient enrollment in a multi-dose Phase 1 clinical trial of FT538 in combination with certain monoclonal antibodies targeting EGFR, HER2, and PDL1 for the treatment of solid tumors.
About Fate Therapeutics’ iPSC Product Platform
About Fate Therapeutics, Inc.