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Taking even the most promising therapy and moving it out of the lab and into people is an incredibly complex process and usually requires a great team. Now, two great teams have paired up to do just that with a therapy for type 1 diabetes (T1D). ViaCyte and CRISPR Therapeutics have put their heads together and developed an approach that has just been given clearance by Health Canada to start a clinical trial.
Regular readers of this blog know that CIRM has been a big supporter of ViaCyte for many years, investing more than $72 million in nine different awards. They have developed an implantable device containing embryonic stem cells that develop into pancreatic progenitor cells, which are precursors to the islet cells destroyed by T1D. The hope is that when this device is transplanted under a patient’s skin, the progenitor cells will develop into mature insulin-secreting cells that can properly regulate the glucose levels in a patient’s blood.
One of the challenges in earlier testing was developing a cell-based therapy that could evade the immune system, so that people didn’t need to have their immune system suppressed to prevent it attacking and destroying the cells. This particular implantable version sprang out of an early stage award we made to ViaCyte (DISC2-10591). ViaCyte and CRISPR Therapeutics helped with the design of the therapeutic called VCTX210.
In a news release, Michael Yang, the President and CEO of ViaCyte, said getting approval for the trial was a major milestone: “Being first into the clinic with a gene-edited, immune-evasive cell therapy to treat patients with type 1 diabetes is breaking new ground as it sets a path to potentially broadening the treatable population by eliminating the need for immunosuppression with implanted cell therapies. This approach builds on previous accomplishments by both companies and represents a major step forward for the field as we strive to provide a functional cure for this devastating disease.”
The clinical trial, which will be carried out in Canada, is to test the safety of the therapy, whether it creates any kind of reaction after being implanted in the body, and how well it does in evading the patient’s immune system. In October our podcast – Talking ‘Bout (re)Generation – highlighted work in T1D and included an interview with Dr. Manasi Jaiman, ViaCyte’s Vice President for Clinical Development. Here’s an excerpt from that podcast.
The Stem Cellar 
For PEC-OT, ViaCyst’s propriety Cy749 pluripotent stem cell line specifically engineered to avoid destruction by the patient’s immune system, and hence cells are being designed to be immune evasive. This designing cells is in favor of eliminating the need for immunosuppressants. Indeed, engineered allogenic stem cells are able to differential into pancreatic endoderm cells and allow direct interaction between blood vessels and implanted cells. This commercialize gene-edited allogenic stem cells ,hopefully can be widely used in future for cells derived therapy.
The safety and efficacy of VCTX210 require further observations to make sure long-term benefit to patients with type1 diabetes. 1)Most genetically modified cells have unstable genotype. Although, they may provide short-term benefits to patients with cell-based therapy. The engineered cells take time to turn around into cancerous cells, this may pose long-term serious health issue and life-threatening to patients. 2)In nature, adult vertebrates require processes of development and tissue maintenance for replenishment of skin, intestine and the hematopoitic stem cells. They require stem cells to proliferate further to produce the functionally mature, postmitotic cells for replacing those lost through natural processes. The stem cells themselves are capable of self-renewal to replace those that become committed to differentiation. During the process of cell proliferation and differentiation lead to rapid production of abnormal cells which are removed by autoimmune response. Hence, engineered allogenic stem cells with ability of immune evasive face high risk of developing cancerous cells. 3)Tissues and organs of human’s body are frequently exposed to rapid changes of pH, body temperature, toxic compounds and inflammatory elements. The engineered cells are not protected by devise of pouch may easily lose its stability of cell genotype and phenotype.
Therefore, patients required long-term follow up to determine their health issues . Both safety and efficacy of cell-based therapy are paramount importance to safeguard long-term benefit of patient’s health and life.