Fate Therapeutics said today it will develop off-the-shelf, chimeric antigen receptor (CAR)-targeted natural killer (NK) cell cancer immunotherapies through a research collaboration with the University of California, San Diego.
The collaboration—whose value was not disclosed—will be led by Dan S. Kaufman, M.D., Ph.D., director of cell therapy at UC San Diego School of Medicine and a professor of medicine in the school’s Division of Regenerative Medicine.
On November 30, Dr. Kaufman was 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.
At the 59th American Society of Hematology (ASH) Annual Meeting and Exposition on December 9, Dr. Kaufman and Fate Therapeutics are scheduled to present preclinical data 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, Dr. Kaufman and Fate Therapeutics had shown that a single dose of CAR-targeted NK cells derived from iPSCs engineered with the CAR construct significantly inhibited tumor growth and increased survival compared to NK cells containing a CAR construct commonly used for T-cell immunotherapy.
That finding was contained in a study published in the October issue of the journal Cancer Research detailing preclinical research for Fate Therapeutics’ first-in-class adaptive memory natural killer (NK) cell product candidate, FATE-NK100.
FATE-NK100 is comprised of adaptive memory NK cells expressing CD57, a marker of NK cell maturation, and the memory-like activating receptor NKG2C. The study offered the first demonstration of a GMP-compatible manufacturing process that induces both NK cell expansion and acquisition of CD57. Higher frequencies of CD57+ NK cells in the peripheral blood or tumor microenvironment in cancer patients have been linked to better clinical outcomes, Fate Therapeutics said.
“Several” Constructs Identified
“We have now identified several CAR constructs optimized for NK cell signaling, persistence, and cytotoxicity, and combined our targeting content with Fate Therapeutics’ iPSC product platform for development of off-the-shelf CAR-targeted NK cell products using clonal engineered master pluripotent cell lines,” Dr. Kaufman said in a statement.
The CAR constructs, according to Fate Therapeutics, 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 the CAR constructs, adding that it maintains an option to exclusively license IP arising from all research and development activities under the collaboration.
The iPSC product platform is designed to enable the company to genetically engineer, single-cell isolate, and select iPSCs for clonal expansion as master iPSC lines.
“We direct the fate of master iPSC lines to create cells of the immune system, including NK cells, T cells, and CD34+ cells, and are advancing a pipeline of off-the-shelf cellular immunotherapies derived from master iPSC lines,” Fate Therapeutics states on its website. “Master iPSC lines are an ideal source for creating cell therapy products that are well-defined, uniform in composition, have a consistent and dose-dependent pharmacology profile, and can be delivered off-the-shelf for the treatment of large numbers of patients.
Fate Therapeutics detailed the working of its iPSC product platform in a study published March 11, 2014, in the journal Stem Cell Reports: “The simplicity and robustness of the system allow for the high-throughput generation and rapid expansion of a uniform human iPSC product that is applicable to industrial and clinical-grade use.”
The platform is supported by an IP portfolio of more than 90 issued patents and 100 pending patent applications that the company owns or licenses.