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Forging a New Partnership in the Fight Against Diabetes

Forging a New Partnership in the Fight Against Diabetes

We are excited to announce that iTolerance, a highly innovative medicine company at the forefront of the battle against T1D, has formed a strategic partnership with the DRI, combining iTolerance’s groundbreaking technology with DRI’s scientific expertise to create a synergy that holds immense promise for patients with T1D.

Revolutionizing T1D Treatment

iTolerance is a biotech startup dedicated to developing regenerative medicine solutions that eliminate the need for lifelong immunosuppression during tissue, organoid, or cell therapy. Their patented technology, known as SA-FasL microgel, has the potential to transform the way we approach T1D treatment. This substance causes the T cells that would attack the transplanted islets to self-destruct. It can also turn the area into an “immune privileged site,” allowing the islet cells to do their work unmolested by the patient’s immune cells.

Meet iTOL-102: A Potential T1D Cure

The flagship program at iTolerance, iTOL-102, is a beacon of hope for those affected by T1D. This program involves the use of allogeneic stem cell-derived pancreatic islets, capable of secreting insulin in response to glucose, in the same manner as native pancreatic cells. What sets iTOL-102 apart is the
application of the SA-FasL microgel platform, which creates localized immune tolerance, “tricking the immune system to accept the transplanted cells as their own.” The hope is that this will work without the need for any general immunosuppression, enabling the long-term survival and function of these implanted cells.

Addressing a Critical Unmet Need

iTolerance’s innovative approach offers hope for the future treatment of T1D by providing a potential cure without the need for lifelong immunosuppression. This advance could lead to an inexhaustible supply of insulin-producing cells while greatly enhancing the quality of life for those affected by T1D.

The iTolerance approach relies on a breakthrough technology that was developed by the DRI team led by Dr Camillo Ricordi: the BioHub project. This unprecedented research resulted in the successful clinical translation of a method to bioengineer an endocrine pancreas within a biodegradable biologic scaffold,
placed onto the omentum (a large flat adipose tissue layer on the surface of the intra-peritoneal organs). This advancement resulted in the first-in-human successful islet transplants into a site outside the liver which is historically where insulin producing islet cells have been transplanted, which was showcased by the DRI team in The New England Journal of Medicine.

The BioHub strategy was developed to combine the novel bioengineering technology with strategies to avoid anti-rejection drugs, eventually applying them to an unlimited source of insulin producing cells. Parallel clinical trials are being conducted at the DRI and other centers in North America and Europe, with such stem cell derived islets.

Camillo Ricordi, Director of the Cell Transplant Center and Director Emeritus of the DRI said, “I am very pleased to see that the three pillars of the DRI BioHub strategy, namely development of a novel transplant site (omentum), transplantation without immunosuppression and unlimited sources of stem cell derived islets, are entering the final stage of clinical translation and rigorous scientific validation. This represents the convergence of over two decades of pioneering work at the DRI, which has now been integrated into iTolerance’s SA-FasL microgel technology.”

iTolerance and DRI are on the brink of initiating their first clinical trial to test iTOL-102. This marks a significant milestone in the fight against T1D, as we move research into real-world applications that bring us closer to a cure.

iTOL-100 platform technology comprises a chimeric fusion protein of streptavidin-FasL which is combined with a biotin-PEG microgel (SA-FasL microgel) to induce local immune tolerance. Fas Ligand (FasL) is a naturally occurring protein that is present in all mammals allowing the establishment of local immune tolerance.

Ordinarily, activated T-cells will reject foreign tissue, such as an islet transplant. That is why current implantation of cells or organs requires life-long immunosuppression of the recipients to prevent organ rejection. Mixing iTOL-100 with the pancreatic islets, and implanting the combination into the body, results in the binding of FasL to the Fas receptor (FasR) on activated T-cells that arrive at the site of islet transplantation to attack them. Rejection is prevented and tolerance induction without continuous recipient immunosuppression results from the elimination of the attacking immune cells by the FasL, through a process called apoptosis (or programmed cell death). In parallel, T-regulatory cells are generated creating long-term localized immune tolerance that protects the implanted insulin producing cells.

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