Engineered immune cells prevent type 1 diabetes in mouse study
Researchers at the University of Arizona have adapted a form of cancer immunotherapy to develop a new potential treatment for type 1 diabetes. In mouse studies, the team tweaked immune cells to fight off the rogue T cells that damage insulin-producing cells in the pancreas, preventing diabetes from developing.
Our immune system is an incredibly powerful machine, sending out various immune cells to patrol the body and destroy bacteria, viruses and other potentially dangerous invaders. But unfortunately sometimes it gets its wires crossed and begins attacking healthy cells instead, which can lead to a range of autoimmune diseases.
Type 1 diabetes is one such disease, triggered when rogue T cells attack and destroy beta cells in the pancreas. Since these cells produce insulin, the resulting shortage of the hormone renders the patient unable to regulate their blood sugar levels, resulting in the health problems associated with diabetes.
Now, researchers on the new study may have a novel tactic to prevent the disease from taking hold in the first place. The team engineered T cells that could target and destroy the misbehaving immune cells, and prevent them from damaging the vital beta cells.
In designing their new T cell, the team mimicked the structure of killer T cells, which hunt their prey using a receptor, coreceptor, and three signaling modules. They named the end result a five-module chimeric antigen receptor (5MCAR) T cell.
"The 5MCAR was an attempt to figure out if we could build something by biomimicry, using some of evolution's natural pieces, and redirect T cells to do what we want them to do,” says Michael Kuhns, lead author of the study. “We engineered a 5MCAR that would direct killer T cells to target autoimmune T cells that mediate type 1 diabetes. So now, a killer T cell will actually recognize another T cell. We flipped T cell-mediated immunity on its head.”
The team tested the treatment in a mouse model of diabetes. Sure enough, the 5MCAR T cells successfully attacked and destroyed the animals’ autoimmune CD4+ T cells, mitigating their diabetes.
"When we saw that the 5MCAR T cells completely eliminated the harmful T cells that invaded the pancreas, we were blown away," says Thomas Serwold, co-author of the study. "It was like they hunted them down. That ability is why we think that 5MCAR T cells have tremendous potential for treating diseases like type 1 diabetes.”
As intriguing as these early results are, it’s important to keep in mind that as with any mouse study there’s no guarantee the effects will carry across to humans. The method is similar to CAR T cell immunotherapy, which uses supercharged immune cells to fight cancer, but the results so far have been mixed.
CAR T cell therapy has been approved by the FDA for use in treating blood cancers, and while early results have been very promising, several deaths during clinical trials have raised concerns. Research continues to find ways to hopefully make the treatment safer and more effective, and as the new study shows, may extend its use to other diseases.
The research was published in the journal Proceedings of the National Academy of Sciences. The team describes the work in the video below.
Source: University of Arizona