Transplantation, Endocrine, Immunology
Novel Fusion Protein Induced Immune Tolerance for Pancreatic Islet Transplantation
2023 Harrington Scholar-Innovator
In hyperglycemia (diabetes), endocrine “islet” cells in the pancreas produce insufficient insulin or cannot use it effectively. Currently, no cure exists, and for 37 million Americans with Type 1 and Type 2 forms of the disease, pharmaceutical insulin becomes a lifeline. Dr. Galipeau and his team are working on restoring normal pancreatic functioning using a genetically-engineered, tolerogenic islet graft approach, with the aim of developing a diabetes cure.
“Our invention concept is based on how placenta allows pregnancy to continue even though the mother and the baby in her womb are separate organisms,” explains Dr. Galipeau. “We copied nature by synthetically encoding a gene for PIDO, a synthetic fusion protein consisting of programmed death-ligand 1 (PD-L1) and indoleamine dioxygenase (IDO) that allows transplanted tissue to evade immune response. In our diabetic mouse model studies, pancreas islet allografts gene modified to express PIDO were not rejected even though no immunosuppressive drugs were given. The grafts reversed hyperglycemia and, importantly, remained functionally viable long term.”
Harrington support and guidance is enabling the team to test clinical grade human stem cells engineered to make PIDO protein and differentiate into synthetic islet cells in mice. Based on previous cross-species animal modeling studies, Dr. Galipeau is optimistic. The process also has significant advantages over other recent experimental graft technologies designed for immune tolerance.
“PIDO-equipped islets, which are tolerated, avoid immunosuppression complications, and can be produced at high volume, could standardize the therapy and make off-the-shelf grafts a reality for diabetics,” Dr. Galipeau says. “We hope to fill a void in tolerogenic immunotherapy and dramatically change the lives of millions of individuals.”