Testing the safety of immunotherapy in diabetes

Diabetes occurs when the T cells of the immune system destroy beta cells in the pancreas that produce insulin. Diabetes researchers have long been interested in using immunotherapy techniques to tamp down this wayward immune activity, but they’ve worried that they’ll accidentally make the disease worse.

Now, a research team led by Cardiff University School of Medicine in the U.K. is testing a technique that targets the destructive T cells—in essence holding them back so they can’t destroy beta cells. And they’re reporting that the technique proved safe and appeared to be effective in a small placebo-controlled trial.

The therapy employs a proinsulin peptide, which activates the immune system’s regulatory T cells (Tregs). These T cells then go out and restrain the beta cell destroying T cells, which are known as effector T cells. In the trial, 27 patients who were newly diagnosed with diabetes received either a placebo or injections of the immunotherapy treatment every two or four weeks for six months.

During the trial, all of the patients on the placebo had to increase their insulin doses over the full year during which participants were tracked. But those on the immunotherapy did not need to change their insulin regimen. The researchers reported their results in the journal Science Translational Medicine. They are planning larger studies to better get a handle on effectiveness, but researchers believe the safety of the treatment shows that immunotherapy could, in fact, be feasible for Type 1 diabetes.

Immunotherapy has taken off in cancer care, where all of the focus has been on arming T cells with the ability to recognize and kill tumor cells. Using immunotherapy in diseases like diabetes is an entirely different challenge, however—one that requires figuring out how to tame an overactive immune system without causing toxic side effects.

In diabetes, much of the immunotherapy research is aimed at finding ways to activate Tregs. At Massachusetts General Hospital, for example, scientists are studying an old tuberculosis vaccine, bacillus Calmette-Guérin (BCG), in patients with Type 1 diabetes. In June, they presented evidence that repeat vaccination with BCG seems to turn on key Treg genes permanently. In a phase 1 trial, BCG produced a slight uptick in insulin secretion.

In July, Eli Lilly placed a big bet on Tregs, laying out $150 million to co-develop Nektar Therapeutics’ NKTR-358, which boosts both the quantity and activity of the beneficial immune cells. Nektar has predicted the drug could prove effective not just in type 1 diabetes, but also in multiple sclerosis, psoriasis, lupus and more.