Researchers have effectively cured type 1 diabetes in mice with pancreatic beta-cell, target-specific, chimeric antigen-receptor (CAR) regulatory T cells (Tregs) and established the viability of their method for treating the disease in humans.
Juan Carlos Jaume of the University of Toledo in Toledo, Ohio, led the study, which was presented at ENDO 2022, the Endocrine Society’s annual meeting in Atlanta, Georgia.
In the past, adoptive cell transfer therapies with CAR cytotoxic T cells have been successful at treating blood cancers. Using non-cytotoxic, anti-inflammatory Tregs instead of cytotoxic, anti-inflammatory Tregs, Jaume and his team attempted to reproduce an equally effective experimental treatment for type 1 diabetes.
“The purpose of this study was to determine if pancreatic beta-cell, target-specific, human CAR Tregs could also identify human pancreatic beta cells (target) and home to human pancreatic islets (where beta cells live) in culture as they do in mice undergoing CAR Treg treatment for T1D,” Jaume explained.
The researchers took blood one to two weeks before pancreas surgery, then collected a small piece of pancreas (5 cc wedge) after it was removed for a clinically approved cause (cancer or pancreatitis).
They started by isolating Tregs from blood samples and growing them in vitro. Those cells were genetically engineered to express a beta-cell-specific CAR along with a GFP marker.
Second, the researchers separated the islets from the pancreas tissue.
The human pancreatic islets were then co-cultured with beta-cell, target-specific CAR Tregs.
Confocal microscopy showed that the GFP positive CAR Tregs successfully migrated into the pancreatic islets within 24 hours. Furthermore, after 72 hours of direct contact with the pancreatic islets, the CAR Tregs multiplied considerably.
“Ours is the first successful, pancreatic beta-cell, target-specific CAR-Treg treatment of T1D in a humanized mouse model that closely resembles the human disease,” said the lead author.
“Based on our mice and human in-vitro data,” added Jaume, “we believe treatment with pancreatic beta-cell, target-specific, CAR-Tregs will allow for recovery and reconstitution of beta cells in human T1D patients as well.”
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