Editas Medicine Reports Engineered iNK Cell Preclinical Data at American Association for Cancer Research Annual Meeting
Preclinical data demonstrate that edited iNK cells result in increased persistence, enhanced anti-tumor activity and extended survival supporting continued development as a novel therapeutic approach for solid tumors
In vivo preclinical data show that edited iNK cells in combination with trastuzumab resulted in complete tumor clearance in 6 of 8 treated mice, as well as prolonged persistence with 100% of treated mice surviving through the end of the experiment (day 144)
The poster reports that the Company generated gene edited iPSC clones, which were then differentiated into iNK cells and assessed for in vitro and in vivo anti-tumor activity. iPSCs were edited at an essential gene exon using both the Company’s proprietary SLEEK (SeLection by Essential-gene Exon Knock-in) technology and engineered AsCas12a nuclease to knock-in both CD16 and membrane-bound IL-15 (mbIL-15). Edited iNK cells (CD16+/+/mbIL-15+/+) were designed to increase antibody-dependent cellular cytotoxicity (ADCC), when combined with tumor-targeting antibodies, and prolong iNK cell persistence in vivo.
“By using our proprietary engineered AsCas12a nuclease and SLEEK technology, we have developed novel allogenic iNK cell lines with significantly enhanced in vitro and in vivo anti-tumor activity, prolonged cell persistence, and resulting increased survival in a murine cancer model,” said
Key findings include:
- Edited iNK cells in combination with trastuzumab showed significantly enhanced tumor killing compared with wild type (WT) iNKs in an in vitro 3D SKOV-3 ovarian tumor spheroid assay.
- Evaluation in an in vivo mouse solid tumor SKOV-3 cancer model demonstrated that edited iNK cells combined with trastuzumab induced significant reduction in tumor burden compared with WT iNK cells plus trastuzumab and trastuzumab only, resulting in complete tumor clearance in 6 of 8 treated mice over the course of the 144-day experiment.
- Additionally, when combined with trastuzumab, edited iNKs significantly increased survival over WT iNK cells in the solid tumor SKOV-3 mouse model. At day 144, 100% of edited iNK-treated mice were alive, compared with less than half of the WT iNK-treated mice.
- Edited iNKs were detected in the peritoneum of the treated mice through the end of the experiment at day 144, demonstrating that the knocked-in mbIL-15 maintained iNK survival for a prolonged period in the absence of exogenous cytokine support.
Presentation Session Information:
Title: AsCas12a gene-edited iPSC-derived NK cells constitutively expressing CD16 and membrane-bound IL-15 demonstrate prolonged persistence and robust anti-tumor activities in a solid tumor mouse model
Date and Time:
Session Category: Immunology
Session Title: Adoptive
Location: New Orleans
Full details of the
About SLEEK Gene Editing
SLEEK (SeLection by Essential-gene Exon Knock-in) gene editing is an optimized approach to developing the next generation of cell therapy medicines for cancer and other serious diseases. Utilizing Editas Medicine’s proprietary engineered AsCas12a nuclease, SLEEK enables high efficiency, multi-transgene knock-in of induced pluripotent stem cells (iPSCs), T cells, and natural killer (NK) cells while ensuring robust, transgene expression.
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Contacts: MediaCristi Barnett (617) 401-0113 cristi.barnett@editasmed.com InvestorsRon Moldaver (617) 401-9052 ir@editasmed.com
Source: Editas Medicine, Inc.
