CAMBRIDGE, Mass., Nov. 12, 2021 — Editas Medicine, Inc. (Nasdaq: EDIT), a genome editing company, announced preclinical data on its progress in the development of novel engineered induced pluripotent stem cell (iPSC)-derived natural killer cells (iNKs) for the treatment of cancer. In the presentation, the Company showed a new method to achieve high-levels of expression of CD16 and Interleukin-15 (IL-15) in iNK cells by using the Company’s proprietary CRISPR/Cas12a-mediated SLEEK (SeLection by Essential-gene Exon Knock-in) technology to simultaneously knock-in both functional genes. The modifications resulted in improved serial tumor killing and dramatically increased NK cell persistence. The Company reported these findings in a poster presentation today at the Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting being held in Washington, D.C., and virtually.
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 Mark S. Shearman, Ph.D., Executive Vice President and Chief Scientific Officer, Editas Medicine.
Shearman continued, “NK cells are great candidates for off-the-shelf immunotherapy medicines given their high tumor killing capacity and their low propensity for graft-versus-host disease, and we believe these data provide evidence for the potential of future experimental medicines from our iNK program to exert enhanced anti-tumor activity in the clinic in the treatment of solid tumors.”
Full details of the Editas Medicine presentation can be accessed in the Posters & Presentations section on the Company’s website.