Editas Medicine Presents Preclinical Data on Novel Engineered iPSC-derived NK Cells for the Treatment of Cancer at the Society for Immunotherapy of Cancer 36th Annual Meeting
In these experiments, iPSCs were edited using the Company’s SLEEK gene editing technology at the GAPDH locus with a proprietary, Editas-engineered AsCas12a nuclease to knock-in high-affinity CD16 and membrane bound IL-15. iPSC clones were then differentiated into iNKs that were confirmed to express high levels of CD16 and IL-15. Increasing NK cell CD16 expression can improve anti-tumor activity when combined with antibody-dependent cell-mediated cytotoxicity (ADCC)-enabling antibodies. IL-15 is important for NK cell survival, and increasing IL-15 expression prolongs the persistence of NK cells. Knock-in of IL-15 may also eliminate the need to administer cytokines systemically, which can cause severe toxicity.
Results demonstrated that the edited iNK cells exhibited enhanced serial tumor cell killing through ADCC in a2D assay against SKOV-3 ovarian cancer cells and in a 3D tumor spheroid killing assay. The edited iNK cells were also able to persist for a dramatically longer period of time relative to unedited iNK cells. Together, these data provide strong support for the continued development of engineered iPSC derived iNK cells as a potential novel class of therapeutics targeting solid tumors.
“In this promising new research, we demonstrate the use of our proprietary SLEEK technology to knock-in both CD16 and IL-15 into iNK cells. The engineered cells demonstrated potent anti-tumor activity and substantially increased persistence without systemic cytokines, an important limitation with many existing NK cell approaches. We also believe this to be a potentially safer and more reliable approach to developing next generation NK cell therapy medicines because through our iPSC development process, we only select cell clones that have exactly the desired on-target edits, thereby avoiding the possibility of cell abnormalities being introduced,” said
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