Editas Medicine Reports Preclinical Data Demonstrating Robust Tumor Reduction and Clearance Using Novel, Engineered iNK Cells at the American Society of Hematology Annual Meeting
Preclinical data demonstrating Editas-engineered AsCas12a multiplexed editing of iPSCs enhances iNK tumor killing ability, supporting promise as a potential therapeutic approach for solid tumors
iNKs with double knock-in of CD16 and mbIL-15 in combination with monoclonal antibody
significantly reduce tumor burden
iNKs with double knock-out of CISH and TGFβR2 substantially reduce tumor burden
The research evaluated two strategies to generate engineered iPSC clones, which were then differentiated into iNK cells and evaluated in vitro and in vivo to determine anti-tumor activity. These approaches have the potential to create allogeneic, investigational NK cell therapy medicines with enhanced activity against solid tumors.
CD16+/+/mbIL-15+/+ Double Knock-in (DKI) Approach
IPSC’s were edited at the GAPDH locus using 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). CD16+/+/mbIL-15+/+ edits were designed to increase antibody-dependent cellular cytotoxicity (ADCC) when combined with tumor-targeting antibodies and prolong iNK cell persistence.
DKI iNK cells, as monotherapy or 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 SKOV-3 cancer model confirmed that DKI iNKs combined with trastuzumab exerted greater anti-tumor activity compared to WT iNKs with trastuzumab, or trastuzumab alone. A single dose of DKI iNKs combined with three doses of trastuzumab induced complete tumor clearance in 50 percent of mice (n=4/8). Importantly, DKI iNKs were detected in the peritoneum of the treated mice for greater than three (3) months, demonstrating that the mbIL-15 maintained iNK survival for a prolonged period in the absence of exogenous cytokine support.
CISH-/-/TGFβR2-/- Double Knock-out (DKO) Approach
In a separate study, iPSCs were edited with Editas-engineered AsCas12a to knock out both the CISH and TGFβ-receptor 2 (TGFβR2) genes. CISH-/-/TGFβR2-/- edits were designed to improve iNK cell effector function and provide resistance to TGFβ-mediated NK suppression in the tumor microenvironment. DKO iNKs induced enhanced tumor killing against in vitro 3D SKOV-3 ovarian tumor spheroids compared to WT iNKs. Following stimulation, DKO iNKs produced elevated levels of inflammatory cytokines, including IFN-γ and TNF-α. The DKO iNK cells also induced significant reduction in tumor burden compared with WT iNK treatment when tested in vivo in a SKOV-3 ovarian cancer mouse model.
“In this promising research, we demonstrate the use of our proprietary engineered AsCas12a nuclease and SLEEK technology with its high efficiency, multi-transgene editing capability to enable the efficient development and evaluation of multiple iNK therapeutic approaches. Using selective, double knock-in and double knock-out strategies, we have developed allogenic iNK cell lines with substantially enhanced in vitro and in vivo anti-tumor activity, reducing or eliminating tumors in tumor-bearing mice. The potency of both modified iNK cell therapeutic approaches supports their continued development as novel cell-based medicines for the treatment of cancer,” said
At ASH, the Company also presented preclinical data on EDIT-301 supporting its differentiated approach to develop a transformative medicine for people living with transfusion-dependent beta-thalassemia (TDT). AsCas12a edited TDT erythroid cells had improved maturation, health, and higher total hemoglobin content per cell when compared to unedited controls. The EDIT-301 Phase 1/2 RUBY trial for the treatment of sickle cell disease is currently enrolling study participants and the Company expects to begin dosing in the first half of 2022.
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.
As a leading genome editing company,
This press release contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "target," "should," "would," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of the Company’s product candidates; availability and timing of results from preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products and availability of funding sufficient for the Company’s foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption “Risk Factors” included in the Company’s most recent Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission, as updated by the Company’s subsequent filings with the
Cristi Barnett(617) 401-0113 firstname.lastname@example.org Investors Ron Moldaver(617) 401-9052 email@example.com
Source: Editas Medicine, Inc.