On February 23, 2018 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that the California Institute for Regenerative Medicine (CIRM) awarded the Company a $4.0 million grant to advance FT516 into a first-in-human clinical trial (Press release, Fate Therapeutics, FEB 23, 2018, View Source [SID1234524183]). FT516 is being developed by Fate Therapeutics as an off-the-shelf engineered NK cell cancer immunotherapy. The NK cell product candidate is derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to uniformly express a novel CD16 Fc receptor.

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"CIRM is pleased to support the continued development of FT516 and Fate Therapeutics’ first-of-kind approach to off-the-shelf cancer immunotherapy using clonal master iPSC lines, which can serve as a renewable cell source for large-scale, cost-effective manufacture of well-characterized, uniform cell products," said Maria T. Millan, M.D., President and CEO of CIRM. "The adoptive transfer of healthy allogeneic donor NK cells has been shown to be well tolerated in patients and has not been associated with the known risks of allogeneic T-cell immunotherapy such as graft-versus-host disease. This suggests that FT516 can be reliably administered without individual patient matching restrictions and used off-the-shelf to treat a large patient population."

NK cells play a critical role in the prevention and treatment of cancer. NK cells naturally express CD16, a potent activating receptor that enables binding of NK cells to the Fc portion of IgG antibodies. Once activated through CD16, NK cells can lyse antibody-coated tumor cells and can secrete immune signaling cytokines, such as interferon gamma, to orchestrate a broad adaptive immune response. Unfortunately, the expression of CD16 on NK cells can undergo considerable down-regulation in cancer patients, which can lead to loss of NK cell anti-tumor activity.

FT516 expresses a novel CD16 Fc receptor that has been modified to prevent the receptor’s down-regulation and to enhance its binding affinity to IgG antibodies. In preclinical studies conducted by the Company, FT516 exhibited potent and persistent anti-tumor activity in vitro and in vivo in multiple tumor cell recognition and killing assays, including in combination with various IgG antibodies.

"FT516 has the potential to address a significant unmet need for more efficacious treatments across multiple solid-tumor types by restoring a patient’s immune cell function and enhancing the therapeutic effect of monoclonal antibody therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We are honored that CIRM has recognized the potential therapeutic value of FT516 as well as the unique advantages of using clonal master iPSC lines to manufacture a well characterized, uniformly engineered cell product in large batches for off-the-shelf use."

The Company plans to develop FT516 for the treatment of multiple tumor types, both as a monotherapy and in combination with tumor-targeting monoclonal antibody therapy. The first-in-human study is expected to evaluate the safety and tolerability of multiple dosing cycles of FT516 in combination with FDA-approved monoclonal antibody therapy.

Fate Therapeutics has built an extensive intellectual property portfolio broadly covering the generation and engineering of iPSCs and the production of NK and T-cell cancer immunotherapies from clonal master iPSC lines. Its proprietary portfolio includes compositions and methods for making iPSCs, including engineering their biological properties using CRISPR and other nucleases, and for producing cells of the hematopoietic lineage, including NK cells, from iPSCs. In addition, the Company has an exclusive license from the University of Minnesota covering iPSC-derived NK cells expressing targeting receptors, including modified CD16 Fc receptors and chimeric antigen receptors for human therapeutic use.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables large-scale generation of off-the-shelf, engineered, 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. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event, and selecting a single iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used for the manufacture of monoclonal antibodies, clonal master iPSC lines can serve as a renewable cell source for the consistent and repeated manufacture of homogeneous cell products with the potential to treat many different diseases and many thousands of patients in an off-the-shelf manner. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 90 issued patents and 100 pending patent applications.