Problem: Colorectal cancer (CRC) is the third most prevalent cancer and the second leading cause of cancer mortality worldwide. In advanced stages, 5-year-survival rates are below 15%. Besides their low efficacy, current therapies often have severe side effects, decreasing the quality of life of CRC patients significantly.
Solution: Based on human CRC patient data, we identified specific bacteria that are less abundant in CRC patients compared to healthy individuals. When applying these bacteria in mice, they show very high efficacy as a monotherapy in various CRC models as well as in other solid tumor entities through specific activation of CD8+ T-cells. Our aim is to apply these bacterial strains to cancer patients in lyophilized form contained in gastro resistant capsules with colonic release. Additionally, we identified the molecule that is responsible for the immune-activating effect as well as the receptor that is targeted by that molecule. Since our in vivo data shows that activation of this specific receptor is sufficient for provoking a strong anti-tumor immune effect, we aim to develop a small molecule targeting that receptor as a second project.
USP: Our approach is much more effective than current immunotherapy (immune checkpoint inhibitors) in vivo. Furthermore, since our products are based on commensal bacteria or small molecules that target the same receptors as beneficial microbiota, we expect higher safety and better tolerability in comparison with the clinical standard-of-care or therapies currently under development. In contrast to other approaches that are targeting the microbiota, we have identified the mechanism of action of our Live Biotherapeutic Product (LBP) in detail. Our therapies aim at improving treatment efficacy while at the same time minimizing severe side-effects and reducing visits to the hospital. Moreover, our LBP could even be applied to prevent tumor recurrence or to avoid tumor development in risk patients.
We found that specific Clostridiales bacteria, that are reduced in the intestine of CRC patients compared to healthy controls, are sufficient to trigger anti-tumor immune responses in CRC mouse models as well as in models for melanoma, breast and lung cancer (Montalban-Arques et al. 2021). Therefore, we expect that an orally applied therapy with these specific bacteria has potential clinical applicability as anti-tumor therapy.
Our results show that immune infiltration into the tumor is enhanced when the bacteria are applied. This may circumvent the problem of current immunotherapies, by which tumors with low immune-cell infiltration cannot be effectively treated. As this novel therapeutic approach is purely based on commensal bacteria that are abundantly present in healthy individuals, we expect a high safety and tolerability profile, minimizing the side effects compared to current anti-tumor therapies. Moreover, these characteristics could qualify this therapy to be used to both treat and prevent CRC.
We have several pilot projects ongoing to test new proprietary bacterial strains in different solid tumor entities and bacteria-derived metabolites with anti-tumor potential. One of those projects is about to enter pre-clinical development and is based on a bacteria-derived metabolite that shows similar anti-tumor efficacy to our bacterial strains. With the development of our platform, we will be able to combine metagenomics and metabolomics data for the discovery of new candidates and targets.
With the support of InnoBooster we will be able to hire a bioinformatician that will help us develop a discovery platform based on metagenomics and metabolomics data with the aim of finding new bacteria and bacteria-derived products that could be used to treat cancer and potentially other immune-related diseases. The platform would be based on experiences in the discovery of the effective bacterial strains and metabolites, where bioinformatic analyses played a central part. This discovery platform would allow us to significantly scale-up our R&D portfolio and license certain assets to other companies for the clinical development. This would allow us to generate capital for the development of our lead products, making us more independent from third party investments.
Am Projekt beteiligte Personen
Letzte Aktualisierung dieser Projektdarstellung 01.03.2023