Grant Award Details
Preclinical development of an immune evasive islet cell replacement therapy for type 1 diabetes
Type 1 diabetes
<p>ViaCyte is a regenerative medicine company focused on the discovery, development, and commercialization of cell replacement therapies for type 1 and insulin-requiring type 2 diabetes. To produce the cells for ViaCyte’s product candidates, pluripotent stem cells are differentiated to pancreatic endoderm cells (also known as pancreatic precursor cells; PEC-01 cells). Once implanted in animals, PEC-01 cells engraft and mature into glucose-sensing insulin-secreting beta cells. In patients however, PEC-01 cells would be attacked by the immune system as would an allogenic organ transplant. Further, with type 1 diabetes, an autoimmune condition, the misdirected immune response to beta cells would compromise the therapeutic cells. Therefore, PEC-01 cells must be protected from allogeneic and autoimmune responses in order to have the potential to treat diabetic patients. Approaches for immune evasion include implantation within a protective device, immunosuppressive drug treatment, and gene editing to prevent rejection by the host immune system.</p><p>ViaCyte and CRISPR Therapeutics, a leading company in the gene-editing space, are collaborating to use CRISPR/Cas9 to edit immune-modulatory genes in ViaCyte’s CyT49 pluripotent stem cell line that is used to produce PEC-01 cells. The gene edits introduced into the CyT49 cell line result in the absence of HLA class 1 proteins, which are major determinants of allo- and auto-immunity, from the cell surface, and the addition of cell-surface molecules that downregulate immune cells. This cell line, VCTX210, passed all tests for proper editing, lack of off-target editing, and genomic stability. Animal tests with VCTX210 PEC-01 showed a robust insulin-secretion response to injected glucose, as with unedited CyT49 PEC-01. Further studies are ongoing to enable clinical testing of VCTX210 over the next few years.</p>
Grant Application Details
- Preclinical development of an immune evasive islet cell replacement therapy for type 1 diabetes
We will produce a universal donor cell (UDC) line by gene editing an embryonic stem cell line. Cell therapies produced from the UDC line will not be rejected by a patient’s immune system.
The UDC line will address the bottleneck of patient immunity that is currently slowing development of many potential cell therapies. It will first be tested in a type 1 diabetes cell therapy.
Major Proposed Activities
- Produce banks of UDC that are of suitable quality for use in manufacturing therapeutic cells for clinical trials.
- Demonstrate that pancreatic cells produced from UDC and implanted into rodents can secrete insulin in response to glucose.
- Demonstrate that pancreatic cells produced from UDC evade immunity, i.e. are destroyed much less efficiently than the unmodified cells in immunological tests.
- Demonstrate function of a gene added into the UDC as a “safety switch”. This safety gene causes implanted cells to die when a specific drug is taken and is a precautionary part of product development.
Statement of Benefit to California:
The universal donor stem cell line would firstly be used to help the thousands of Californians with insulin-requiring diabetes, but soon thereafter would be applied to other substantially unmet medical needs. Cell therapies have the potential to restore a relatively normal life to patients and their families, extend patients' lives, and dramatically reduce the state's health care burden. This would represent a tremendous achievement and asset for California, its taxpayers, and CIRM.
Source URL: https://www.cirm.ca.gov/our-progress/awards/preclinical-development-immune-evasive-islet-cell-replacement-therapy-type-1