Tired T cells hamper cancer treatment, but could be a boon for diabetes drug

Healthy human T cell. Image: NIAID

While T cell exhaustion can hinder cancer treatments, a Benaroya Research Institute-led team has discovered that T cell fatigue may potentially boost therapies for diabetes and other autoimmune diseases.

Immune T cells burn out and become less effective when they are overworked, so scientists working on cancer immunotherapies are seeking to bypass this phenomenon. But a new study found that T cells with similar qualities to fatigued T cells are associated with a positive response to the diabetes drug Teplizumab.

The researchers, from the Benaroya Research Institute, the Immune Tolerance Network and Yale University, studied 74 patients with Type 1 diabetes, 49 of whom were treated with Teplizumab. The remaining 25 patients served as a control group.

The team found that patients who were particularly responsive to the drug had memory T cells that shared characteristics with tired T cells, including high levels of the transcription factor EOMES and multiple inhibitory receptors, according to the study. The findings prompted the researchers to conclude that T cell exhaustion may contribute to successful immune interventions for Type 1 diabetes.

Teplizumab has had a bumpy ride: Eli Lilly in-licensed the drug from MacroGenics for a whopping $41 million only to pull the plug on its Phase III program when it failed a late-stage trial in 2010. Despite the failure, the anti-CD3 monoclonal antibody found success three years later, proving “strikingly effective” at preserving insulin-producing cells in a trial of 52 newly diagnosed Type 1 diabetics, most of whom were younger than 14.

The study’s results suggest yet another avenue for Teplizumab to rise from the ashes: Weary T cells could be a target for therapies against diabetes and other autoimmune diseases.

Meanwhile, George Washington University researchers have tapped into another facet of T cells in autoimmune disease. In August, they identified transcription factors as a “vital component” in determining the function of a T cell, that is, whether it will become a killer or helper T cell. They hypothesized that transcription factors could be manipulated to skew the T cell ratio in favor of killer cells, thus reinforcing the immune system against autoimmune diseases.