Published 07 December 2017
Fate Therapeutics has partnered with the University of California San Diego to develop off-the-shelf, chimeric antigen receptor (CAR)-targeted natural killer (NK) cell cancer immunotherapies.
The two-year collaboration is being led by Dan S. Kaufman, M.D., Ph.D., Professor of Medicine in the Division of Regenerative Medicine and Director of Cell Therapy at UC San Diego School of Medicine.
“NK cells have the inherent ability to target a diversity of stress-induced ligands on tumor cells and can be safely administered without the need for individualized patient matching. Additionally, NK cells engineered with chimeric antigen receptors can be targeted to tumors with high specificity.
“This duality provides CAR NK cells with the unique potential to overcome antigen escape and address tumor heterogeneity, which are distinct advantages over patient-specific CAR T-cell immunotherapies,” said Dr. Kaufman.
“We have now identified several CAR constructs optimized for NK cell signaling, persistence and cytotoxicity, and combined our targeting content with Fate Therapeutics’ induced pluripotent stem cell product platform for development of off-the-shelf CAR-targeted NK cell products using clonal engineered master pluripotent cell lines.”
The CAR constructs identified by the collaborators contain transmembrane and co-stimulatory domains that enhance antigen-specific NK cell activation and improve the effector function of NK cells.
Fate Therapeutics holds an exclusive license to the intellectual property covering these CAR constructs and maintains an option to exclusively license intellectual property arising from all research and development activities under the collaboration.
At the 59th American Society of Hematology (ASH) Annual Meeting and Exposition, Dr. Kaufman and Fate Therapeutics will present preclinical data on Saturday, December 9, 2017 highlighting CAR-targeted NK cells derived from an induced pluripotent stem cell (iPSC) engineered with a specific CAR construct containing a NKG2D transmembrane domain, a 2B4 co-stimulatory domain and a CD3ζ signaling domain.
In preclinical studies using an ovarian cancer xenograft model, the collaborators have shown that a single dose of CAR-targeted NK cells derived from iPSCs engineered with this specific CAR construct markedly inhibited tumor growth and significantly enhanced survival as compared to NK cells containing a CAR construct commonly used for T-cell immunotherapy.
Dr. Kaufman was recently awarded $5.15 million by the California Institute for Regenerative Medicine (CIRM) to advance clinical translation of NK cells derived from pluripotent stem cells into a standardized treatment for treating hematologic malignancies.
iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The engineering of iPSCs can be done as a one-time genetic modification event and a single iPSC can be selected for creation of a clonal master pluripotent cell line.
Similar to master cell lines used for the manufacture of therapeutic antibodies, a clonal master pluripotent cell line can be used to repeatedly create clonal populations of effector cells. This first-of-kind approach enables large-scale generation of off-the-shelf, targeted, homogeneous cell products that can be administered in repeat doses to mediate more effective pharmacologic activity, including in combination with cycles of other cancer treatments.
Source: Company Press Release