Immunotherapy is a relatively new type of cancer treatment that involves strengthening the immune system and boosting its ability to identify and kill cancer cells. A recent study has found that a type of immunotherapy called checkpoint inhibitors, which prevent checkpoint proteins from binding with partner proteins, can also induce immune-related adverse events (irAEs) in cancer patients.
Although immune checkpoint inhibitors have exhibited significant promise in cancer treatments, checkpoint inhibitor-induced toxicities can affect virtually any organ after treatment. Scientists have now found that colitis is one of the most common and severe toxicities that occur in cancer patients who undergo immune checkpoint inhibitor treatment.
University of Michigan Health Rogel Cancer Center researchers specifically discovered a mechanism that induces severe gastrointestinal problems in cancer patients who go through immunotherapy treatments. The research team found that colitis typically occurs after cancer patients go through checkpoint inhibitor cytotoxic T-lymphocyte protein 4 (CTLA-4). Researchers also found a means of delivering checkpoint inhibitor immunotherapies without the associated immune-related adverse events.
The study was partly funded by the National Institutes of Health (NIH), Canadian Institutes of Health, Crohn’s & Colitis Foundation, Takeda Millennium Pharmaceuticals and the National Science Foundation with support from the Rogel Cancer Center Shared Resources of Single Cell Spatial Analysis, Tissue and Molecular Pathology.
Senior study author and Paul de Kruif Professor of Pathology at Michigan Medicine Gabriel Nunez, MD, says that the research team’s findings were a great example of how understanding underlying mechanisms could help scientists develop more effective alternative therapies. According to Nunez, identifying the mechanism that resulted in the development of colitis allowed researchers to come up with different ways of overcoming such immune-related adverse events without hampering the immunotherapy’s antitumor abilities.
Immune checkpoint inhibitor treatment has proven to be effective at treating several types of cancer, but it can also induce severe side effects, including colitis. Colitis is characterized by inflammation in the colon and causes symptoms such as abdominal pain, urgent diarrhea, bloated stomach, weight loss and appetite loss. In severe cases, cancer patients who develop colitis experience side effects such as anemia, fatigue, dehydration, malnutrition, malabsorption and severe gastrointestinal discomfort.
Many end up discontinuing the treatment due to the colitis-related discomfort.
The Rogel research team created a novel mouse model to study the mechanism and found that the association between gut microbiota composition and a certain domain of immune checkpoint antibodies induced colitis. Removing this domain eliminated treatment-induced colitis while retaining the therapy’s potent antitumor response. The research team will carry out additional studies to expand its understanding of the underlying mechanisms that cause colitis in cancer patients and work toward a clinical trial.
This growing body of knowledge on how immunotherapy can be made a viable option for all cancer patients could boost the efforts of enterprises such as Renovaro BioSciences Inc. (NASDAQ: RENB) currently engaged in immunotherapy R&D.
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