For the 80 million people worldwide with celiac disease, the only treatment available is to cut grains like pasta and bread out of their lives. But researchers are hoping to change that with a new cell therapy that was able to tamp down the immune system’s overreaction to gluten in mouse models.
The study’s results were published in Science Translational Medicine on March 19.
In cultures of both human cells and living mice, engineered regulatory T cells were able to simmer down gluten-reactive effector T cells that cause the characteristic autoimmune response seen in celiac disease.
The researchers, led by immunologist Yannick Muller, M.D., Ph.D., of Lausanne University Hospital and the University of Lausanne in Switzerland, next plan to continue testing the technique in other mouse models of the disease while also moving into human trials.
Gluten is a protein found in grains that is difficult to digest. In people with celiac disease, gluten triggers an intense immune response in the intestines that leads to gastrointestinal symptoms such as stomach pain and diarrhea. With no approved treatments, the only way to avoid symptoms is to stop eating foods that contain gluten.
Muller and his team decided to harness the power of regulatory T cells to hit the brakes on the overreactive anti-gluten immune system response in celiac disease. These cells have proven safe to use in various clinical trials, Muller told Fierce Biotech in an interview, because they don’t require wiping out the existing pool of immune cells with chemotherapy first, the way other cell therapies do.
Celiac disease is also a good candidate for regulatory T-cell therapy because in more than 90% of patients it is caused by a genetic variant called HLA-DQ2.5, Muller added.
“Almost all the patients have the same genetic predisposition and that means you can use T cell receptors to redirect the specificity of the cells,” Muller said. “For many other diseases it’s more complicated because you have a lot of heterogeneity.”
HLA stands for human leukocyte antigen, which are the proteins used by cells to present their contents to the immune system for monitoring. When broken-down bits of gluten are presented on the DQ2.5 variant of HLA, effector T cells react aggressively and cause celiac disease symptoms.
Muller’s team edited the T-cell receptors of regulatory T cells so that they were also activated by gluten, triggering them to perform their function of calming down effector T cells when the protein was present.
Because the researchers did not have access to mouse models of celiac disease, they had to also edit effector T cells in the rodents to make them reactive to gluten. They could then test whether the edited regulatory T cells, the actual intended therapy, were able to suppress the effector T cells.
While Muller wants to do more studies in mice, he also thinks that, given the proven safety of other regulatory T cell therapies, that the approach is ready for human studies. “In my opinion, the data we have collected so far should be sufficient to justify to go further,” he said.
The celiac cell therapy is autologous, meaning cells would have to be taken from a patient, edited and then given back to the same patient. That’s opposed to an allogeneic approach, where the edited cells come from a different person.
The autologous approach is “very costly,” Muller said. Ideally, the team would move toward an allogeneic, off-the-shelf approach, but “that will take time.”