The U.S. Food and Drug Administration (FDA) has granted approval for Fate Therapeutics’ Investigational New Drug (IND) application for FT500. This milestone positions the company to initiate the first clinical trial in the United States investigating a cell product derived from induced pluripotent stem cells (iPSCs). FT500 is a universal, off-the-shelf natural killer (NK) cell product candidate developed from a clonal master iPSC line. Fate Therapeutics announced this breakthrough on November 30, 2018.
In a press release, the company explained, “Our proprietary iPSC product platform enables mass production 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. Our 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.”
Other Advances in iPSC-Derived Cell Therapies
While Fate Therapeutics will lead the first iPSC-derived cell therapy trial in the U.S., similar studies have already been conducted internationally.
In 2014, Masayo Takahashi of Japan’s RIKEN Center launched the world’s first investigation into iPSC-derived cell therapies, focusing on safety in patients with age-related macular degeneration. Although temporarily suspended in 2015 over safety concerns, the trial resumed in 2016 using donor-derived iPSCs.
In 2017, Australia-based Cynata Therapeutics began a Phase I clinical trial of its iPSC-derived mesenchymal stem cell (MSC) product, CYP-001, for graft-versus-host disease (GvHD). By August 2018, it had completed the primary evaluation for 15 patients and is now advancing to Phase II trials targeting critical limb ischemia. More recently, the company has been testing its iPSC-derived MSC product, CYP 004, in a Phase 3 clinical trial involving a staggering 440 patients.
Japan’s Leadership in iPSC Research
Japan remains at the forefront of iPSC-derived therapies, with several physician-led studies underway:
- iPSC-derived Cardiomyocytes for Ischemic Cardiomyopathy: In 2017, iPSC-derived cardiomyocytes were grafted on to a porcine model of ischemic cardiomyopathy using a cell-sheet technique. Cardiac function was significantly improved and neovasculogenesis was observed.
- Platelet Production: Researchers at CiRA aim to produce iPSC-derived platelets, with clinical treatments anticipated to begin in 2019. This process involves creating iPSCs from white blood cells and differentiating them into megakaryocytes, which produce platelets.
- iPSC-Derived Dopaminergic Neurons for Parkinson’s Disease: In October 2018, dopamine precursor cells were created from allogeneic iPSCs produced by Jun Takahashi’s research group at Kyoto University. Physicians at Kyoto University Hospital then transplanted these cells into subjects with Parkinson’s disease. A total of seven patients were involved.
- iPSC-derived Corneal Cells for Limbal Stem Cell Deficiency: In July 2019, scientists at Osaka University started a clinical trial for limbal stem cell deficiency, a condition in which corneal stem cells are lost. The scientists grafted a sheet of iPSC-derived corneal cells onto the cornea of a patient. Within one month, her vision seemed to have improved.
- iPSC-derived Cells for Spinal Cord Injury: Several preclinical studies in spinal cord injuries using iPSC-derived neural progenitor cells in animal models have provided evidence for remyelination and locomotor function recovery. In February 2018, the Japanese government gave an approval to Professor Hideyuki Okano for a clinical trial that will involve the treatment of patients with spinal cord injuries at Keio University.
The question now is how quickly iPSC research will expand globally. What are your thoughts on the future of iPSC therapies? Share your insights in the comments below.