Selected Clostridiales bacteria as novel treatment for solid tumors

Despite the recent advances in cancer research and therapy, including checkpoint blockade immunotherapy, the percentage of patients responding successfully to these treatments is still poor. Cancer is still the second leading cause of death globally, being breast cancer, lung cancer and colorectal cancer (CRC) among the most diagnosed forms of cancer and the leading causes of cancer-related deaths worldwide. Increasing evidence indicates that alterations in the composition of the gut microbiota are associated with an extensive number of inflammatory and malignant diseases, including CRC. In our group we have identified, by a meta-analysis of published studies, specific Clostridiales bacteria strains that are maximally reduced in the intestine of CRC patients compared to healthy people. When orally applied to mice bearing CRC tumors, a mix consisting of four of those strains (CC4) prevented tumor development and shaped the entire intestinal microbiome composition favouring the community of Clostridiales bacteria. On a molecular level, we found that the CC4 mix induces the frequencies and activity of anti-tumor CD8+ cytotoxic T-cells and NK cells only within the tumor tissue, suggesting that the effect of the bacteria might be focused on the tumor and might have only limited local or systemic side effects. Our CC4 mix was show to be equally effective as the clinical standard for CRC therapy, 5-Fluorouracil, and presented a higher efficacy when compared to anti-PD1 checkpoint inhibitor treatment. Interestingly, our CC4 mix showed similar effect in other solid tumor models, such as melanoma, breast cancer and lung cancer. Taking into account our pre-clinical results, we support the idea that bringing this bacteria-based therapy to clinics would be of great benefit for cancer patients. For this purpose, and with the support of the UZH Entrepreneur Fellowship and the SNF/Innosuisse BRIDGE PoC, we aim to develop a lyophilized (freeze-dried) formulation of our bacteria to be tested in our murine models and afterwards, GMP-conform produced bacteria with the final aim of bringing our project into IND-enabling studies, and eventually, to clinical trials.

Our novel approach applying a mix of bacteria as stand-alone cancer therapy is to the best of our knowledge the only therapeutic approach that shows striking efficacy as stand-alone bacteria treatment not only in CRC, but also in all tested cancer models so far. Demonstrating efficacy and safety of our microbiome therapy in cancer patients would signify a true break-through innovation in the field. Moreover, our bacterial-based treatment would have a profound impact in the medical care of cancer