A University of Louisville-born therapy that helps people with Type 1 diabetes stay off immunosuppressants by re-educating the body’s immune system to accept transplanted insulin-producing cells now has a commercial partner.

iTolerance Inc., a San Mateo, Calif.-based biotech company, has signed an exclusive license and intends to develop the therapy toward clinical use. The technology was co-invented at UofL and at the Georgia Institute of Technology with support from the National Institutes of Health and JDRF, which funds Type 1 diabetes (T1D) research.

“Our goal is to help people with Type 1 diabetes, so they don’t have to suffer the side effects that come with immunosuppressants,” said Haval Shirwan, Ph.D, inventor and gratis professor in the UofL Department of Microbiology and Immunology.

In Type 1 diabetes, a condition affecting some 1.6 million Americans, the body’s immune system attacks cells in the pancreas that produce insulin, a hormone that regulates blood sugar. As a result, patients that receive pancreatic islet transplants need to be placed on immunosuppressants and cope with the possible side effects, including loss of appetite, nausea and increased risk of infection.

The technology works by training the immune system to accept insulin-producing cells through transplanted islets — cells taken from the pancreas. The islets are laced with a recombinant protein pioneered by Shirwan and Esma S. Yolcu, Ph.D., a gratis faculty member at UofL, known as Fas ligand (FasL), which “teaches” the immune system to see new graft as beneficial rather than a threat.

Once the immune system has been re-trained, the idea is to transplant healthy islet cells so the patient again can produce insulin on their own.

The UofL scientists teamed up with researchers at Georgia Tech to generate a hydrogel formulation delivering FasL to the graft site to ward off rejection. The technology has the potential to be an “off-the-shelf” treatment, and the hydrogels which hold the islets can be prepared up to two weeks ahead of the transplant. The islets also don’t need to be modified for the individual patient.

“We look forward to leveraging the technology to locally and durably induce immune tolerance of organ transplants,” said Cameron Gray, Ph.D., J.D., founder and chairman of iTolerance. “We believe the technology has potentially far-ranging implications for engraftment."

iTolerance holds an exclusive license to the technology through Georgia Tech and the UofL Commercialization EPI-Center, which works with startups and industry to commercialize university-born technologies.

IMAGE: Immunomodulatory signal presentation via synthetic hydrogel material promotes generation of T regulatory cells (green) in the local graft microenvironment (CD3+ T cells in red, and nuclei staining in blue) after implantation into a clinically relevant transplant model for the treatment of Type 1 diabetes. (Image courtesy Georgia Tech)

August 6, 2020