Researchers Identify Why Cancer Immunotherapy Can Cause Colitis
Published:19 Feb.2024 Source:Michigan Medicine - University of Michigan
Researchers at the University of Michigan Health Rogel Cancer Center have identified a mechanism that causes severe gastrointestinal problems with immune-based cancer treatment. They also found a way to deliver immunotherapy's cancer-killing impact without the unwelcome side effect.
Immune checkpoint inhibitors can cause severe side effects, including colitis. The problem facing researchers was that while patients were developing colitis, the laboratory mice were not. To get past this, the Rogel team, led by first author Bernard C. Lo, Ph.D., created a new mouse model, injecting microbiota from wild-caught mice into the traditional mouse model. In this model, the mice did develop colitis after administration of antibodies used for tumor immunotherapy. In fact, colitis developed because of the composition of the gut microbiota, which caused immune T cells to be hyper-activated while regulatory T cells that put the brakes on T cell activation were deleted in the gut. This was happening within a specific domain of the immune checkpoint antibodies. Researchers then removed that domain, which they found still resulted in a strong anti-tumor response but without inducing colitis.
To follow up what they saw in mice, researchers reanalyzed previously reported data from studies of human cells from patients treated with immune checkpoint antibodies, which reinforced the role of regulatory T cells in inducing colitis. The Rogel team plans additional studies to further understand the mechanisms causing colitis and seeks clinical partners to move this knowledge to a clinical trial.