Induced immune tolerance may reduce the need for long-term immunosuppression
San Diego, California, December 18, 2014 — ViaCyte, Inc. announced today a preclinical study published online in Cell Stem Cell that describes a novel approach to replace the insulin-producing cells that are lost in type 1 diabetes. The approach utilizes pancreatic precursor cells derived from human embryonic stem cells and a pro-tolerogenic therapy that has the potential to allow the cells to survive after transplantation into the host without continuous immunosuppressive therapy. Type 1 diabetes results when a person’s own immune system destroys insulin-producing cells in the pancreas, and replacement of these cells is thought to be an effective way to ameliorate the disease.
The study, conducted by scientists at the University of California, San Francisco (UCSF) and ViaCyte, a privately-held regenerative medicine company, documented in a mouse model that a selective blockade of specific elements of the immune system, co-stimulatory blocking agents CTLA4Ig and anti-CD154, allows the implanted precursor cells to avoid immune rejection and develop into the insulin-producing and other cells of the healthy endocrine pancreas. These cells release pancreatic endocrine hormones such as insulin in response to changes in blood sugar.
Normally, cell transplants from an unrelated donor remain viable only if the recipient’s immune system is suppressed. The new study, published online in advance of the February print edition of Cell Stem Cell, utilized several models including a mouse model that has been “humanized” in the sense that it carries key parts of the human immune system and should respond immunologically to the human cells as would occur after a transplant into a patient, with a promising new technique to gently and selectively dampen T-cell-mediated transplant rejection.
The approach allowed the implanted cells to grow, produce insulin, and form islet structures. The mice, which were treated to chemically eliminate their own insulin-secreting cells, had healthy levels of insulin provided by the implanted human cells, and consequently normal blood sugar levels. The study authors believe that the approach, discovered in normal mice and validated in the humanized mouse model, could be developed into a method that combines cell therapy with the tolerogenic treatment providing a “sustainable alternative strategy for patients with type 1 diabetes.”
The cells used in the experiments were similar to those developed for use in ViaCyte’s VC-01™ product candidate which is currently being studied in the clinic. These pancreatic precursor cells (called PEC-01™ cells) differentiate and mature after surgical implantation into fully functioning insulin-producing beta cells and other endocrine cell types that make up the normal human pancreatic islet, the region of the pancreas that contains insulin. The VC-01 combination product employs a macroencapsulation device that is designed to protect the implanted cells from the patient’s immune system.
Normally, non-encapsulated PEC-01 cells would be immunologically recognized as foreign and eliminated by T cells. However, in the study described here, UCSF and ViaCyte researchers used an emerging therapeutic strategy that stops the rejection process by selectively blocking co-stimulatory signals that T cells must receive in order to initiate rejection.
“The demonstration that these new immunotherapies block specific pathways and immune cells that are responsible for attacking pancreatic islet cells and prevent the rejection of implanted PEC-01 cells is an exciting finding that could lead to advances in the way we treat diabetes and other diseases,” said Jeffrey Bluestone, PhD, who holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Metabolism and Endocrinology at UCSF. “In the future, a short treatment with immunotherapies to produce tolerated immune cells could open the door to a wide variety of practical regenerative medicine approaches.”
Kevin D’Amour, PhD, chief scientific officer at ViaCyte commented, “These findings, should they be verified in human trials, could provide an alternative approach to the treatment of type 1 and insulin-requiring type 2 diabetes with our PEC-01 cells. By interfering with the immune processes that normally lead to recognition of foreign cells, these new immunotherapies may represent a way for the implanted PEC-01 cells to survive and fully mature to islet like structures, producing insulin and other regulatory proteins in order to maintain normal blood sugar levels long-term.”
Over a million people in the United States manage their type 1 diabetes with multiple daily injections of insulin and rigorous management of diet and lifestyle. Islet cell transplantation had been demonstrated to reduce or eliminate the need for insulin injections, but at a high cost: patients require strong immunosuppression for the remainder of their lives, which carries significant side effects, including risks of infections and cancer.
In related research, ViaCyte is currently evaluating the VC-01 product candidate, which is a combination of PEC-01 cells encapsulated within an implantable device that shields the cells from immune-system rejection. A Phase 1/2 clinical trial, called STEP ONE, or Safety, Tolerability, and Efficacy of VC-01 Combination Product in Type 1, is evaluating the VC-01 product candidate for the treatment of type 1 diabetes.
The findings in Cell Stem Cell suggest that immunotherapy may be an alternative to the use of a physical protection device to prevent immune system rejection of the PEC-01 cells.
A Disease Team Research Award and a Transplantation Immunology Award, both from the California Institute for Regenerative Medicine (CIRM), supported the research publication titled, “Tolerance Induction and Reversal of Diabetes in Mice Transplanted with Human Embryonic Stem Cell-Derived Pancreatic Endoderm.”
ViaCyte is a privately-held, clinical-stage regenerative medicine company focused on developing a novel cell therapy for the treatment of diabetes. ViaCyte is conducting a Phase 1/2 clinical trial of the Company’s lead product candidate VC-01 in patients with type 1 diabetes who have minimal to no insulin-producing beta cell function. The VC-01 combination product is based on the production of pancreatic progenitor cells (PEC-01), which are implanted in a durable and retrievable encapsulation device, known as the Encaptra® drug delivery system. Once implanted and matured, these cells are designed to secrete insulin and other regulatory factors in response to blood glucose levels. VC-01 combination product is being developed as a potential long-term diabetes treatment without immune suppression and without risk of hypoglycemia or other diabetes-related complications.
ViaCyte is headquartered in San Diego, California with additional operations in Athens, Georgia. The Company is funded in part by the California Institute for Regenerative Medicine and JDRF. For more information, please visit www.viacyte.com.
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