Even though, according to recent preliminary studies, the risk of dying from cancer has declined within the European Union in recent years, cancers remain among the leading causes of death. However, there has been extremely encouraging progress in some areas, such as the fight against lymphoma using cancer immunotherapies with CAR-T cells. With the help of a genetic engineering process, the body's own T cells can be converted in the laboratory into chimeric antigen receptor T cells (CAR-T cells) and then transferred back into patients. Equipped with these antigen receptors, the modified T cells are then able to seek out and destroy the tumor cells in the body.
Nevertheless, there are still large differences between the treatment results of patients. One possible cause here is the use of antibiotics.
We were able to show that treatment with antibiotics prior to CAR-T cell therapy has a negative effect on the success of cancer immunotherapy."
"Using machine learning, a subfield of artificial intelligence, we were able to identify specific components of the microbiome that allowed us to predict the clinical outcomes of CAR-T cell immunotherapy by focusing on patients who had not previously taken antibiotics," Prof. Elinav explains.
"In the future, components of our gut microbiome, i.e. certain bacteria, could be used as so-called biomarkers to better predict the efficacy of CAR-T cell therapy" adds Prof. Stein-Thoeringer. However, this remains to be seen in further multicenter studies.
In Tübingen, Prof. Stein-Thoeringer is continuing to work on the role of the gut microbiome in immunotherapies against cancer such as CAR-T cell therapy and, in particular, how individual bacteria can influence immune cells and what therapeutic possibilities arise from this. In this context, his professorship is integrated in the Tübingen Cluster of Excellence "Controlling Microbes to Fight Infections" (CMFI).
In addition to the University Hospital Tübingen and the DKFZ in Heidelberg, the international team of experts included researchers from the Weizmann Institute of Science (Israel), University Hospital Heidelberg, the LMU University Hospital Munich, the University Hospital Regensburg, the MD Anderson Cancer Center in Houston (USA) and the Moffitt Cancer Center in Tampa (USA).
Stein-Thoeringer, C. K., et al. (2023). A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy. Nature Medicine. doi.org/10.1038/s41591-023-02234-6.