Researchers identify why cancer immunotherapy can cause colitis

Identification of the Cause of Colitis in Immunotherapy: Researchers identified that severe gastrointestinal problems, specifically colitis, associated with immune-based cancer treatments are caused by the composition of gut microbiota.

Development of a New Mouse Model: To study this side effect, which was not occurring in traditional laboratory mice, the team created a new mouse model by injecting microbiota from wild-caught mice. This model successfully mimicked the colitis seen in human patients undergoing immunotherapy.

Mechanism of Colitis Formation: The study found that colitis developed due to an imbalance in the immune system. This imbalance involved hyper-activation of immune T cells and the deletion of regulatory T cells, which are normally responsible for moderating T cell activation, in the gut.

Modified Immunotherapy Approach: The researchers were able to modify the immune checkpoint antibodies used in immunotherapy. By removing a specific domain from these antibodies, they could prevent colitis while still retaining the strong anti-tumor response.

Future Clinical Applications: The findings have significant implications for improving cancer immunotherapy. The team is planning further studies to understand the mechanisms causing colitis and is seeking clinical partners to translate this knowledge into clinical trials.