Clinical trial of iPSC-derived MSCs for treatment of steroid-resistant Graft-versus-host disease

Mesenchymal stem cells (MSCs), which can be found both in bone marrow and in adipose (body fat) tissue, can be immuno-privleged, meaning they are not readily recognized by the immune system and can survive upon transplantation between immunologically different individuals. Moreover, they can exert significant anti-inflammatory effects that has resulted in their use as a cell-based therapy to treat inflammatory diseases, either by transplantation into a donor’s own diseased tissue or into another recipient. However, there can be great variability in the effectiveness of such donor cells due to differences in their intrinsic physiology. There is also a limit to their ability to expand in number in cell culture.

In an effort to produce a more uniformly effective and limitless source for MSC-based therapy, Cynata Therapeutics under license from Fujifilm has developed a novel induced pluripotent stem cell (iPSC)-derived product, CYP-001, Cymerus™ MSCs for use in cell therapy. iPSCs from a single donor somatic cell have a practically unlimited potential for expansion in cell culture and can readily be differentiated in to MSCs with the same properties, thus providing a consistent and unlimited source of MSCs. In July, 2020, Cynata announced positive results from the two-year follow-up of 15 patients enrolled in the Phase 1 clinical trial (safety and efficacy) of CYP-001 for treatment of blood stem cell transplant patients with a steroid-resistant form of the inflammatory syndrome, Graft-versus-host disease (GvHD).

GvHD is an immune disease that may occur after bone marrow and other tissue transplants where white blood cells of the donor’s immune system, which may remain among the donated cells (the graft) recognize the recipient (the host) as foreign (non-self). The GvHD immune response of the donor cells leads to widespread inflammation of the recipient’s tissues and can lead to high rates of patient mortality if drug treatments are ineffective. One such class of patients who have a poor prognosis and high mortality are those whose GvHD is resistant to treatment with anti-inflammatory steroid drugs.

In the multi-center study, subjects received two intravenous infusions of CYP-001 one week apart at either a low or high dose of cells. Patient responses were evaluated at 28 and 100 days following infusions of cells. In all cases, the treatment was well-tolerated and there were no treatment-related side effects reported. In conclusion, CYP-001 infusions were found to be safe and well-tolerated in this study, and the overall positive treatment response and improved survival rates support the progression to a Phase II trial. The results of the clinical trial were reported in the journal, Nature Medicine, by Bloor and colleagues.

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