Novel Approach to Immunotherapy in Ovarian Cancer
Researchers from the University of Pittsburgh have identified an approach using cytokines produced by Lactobacillus reuteri (LR) to stimulate one of the key proteins (PD-L1) involved in programed cell death in cancer cells to facilitate immunotherapy.
Description
Ovarian cancer (OC) can be a devastating disease, due to rare symptoms resulting in diagnosis often only when cancer is at an advanced stage and has spread. Treatment is challenging and many patients relapse within 6–18 months of surgery and chemotherapy, with the added complication of being resistant to first-line chemotherapy. Effective treatment is urgently required as current therapies for OC are often ineffective with only a 50% survival rate. This approach has the potential to improve outcomes in patients with OC.Applications
• Ovarian cancer immunotherapy• Protection of intestines from radiotherapy
• Mitigate immune dysfunction in victims of radiation terrorism incidents or accidents
Advantages
Treatment options for OC are suboptimal with approximately 150,000 deaths annually in the US. Alone. Additionally, abdominal irradiation is not a feasible treatment approach due to the risk of intestinal damage. This novel approach involves treating OC patients with LR-produced cytokines and acts in two ways. Firstly, protecting the intestine from irradiation through the action of LR-producing IL-22 (LR-IL-22), and secondly, increasing expression of PD-L1 in cancer cells improving the potential of using immunotherapy to treat OC.Invention Readiness
Preclinical studies have shown treatment with LR-IL-22 or LR-IFN- and WAI treatment increase intra-tumoral CD8+ T cells in OC. Development of oral delivery and human trials is required.IP Status
https://patents.google.com/patent/WO2024092131A1Related Publication(s)
Hamade, D. F., Epperly, M. W., Fisher, R., Hou, W., Shields, D., van Pijkeren, J.-P., Mukherjee, A., Yu, J., Leibowitz, B. J., Vlad, A. M., Coffman, L., Wang, H., Huq, M. S., Huang, Z., Rogers, C. J., & Greenberger, J. S. (2023). Release of Interferon-β (IFN-β) from Probiotic Limosilactobacillus reuteri-IFN-β (LR-IFN-β) Mitigates Gastrointestinal Acute Radiation Syndrome (GI-ARS) following Whole Abdominal Irradiation. Cancers, 15(6), 1670. https://doi.org/10.3390/cancers15061670
Hamade, D. F., Espinal, A., Yu, J., Leibowitz, B. J., Fisher, R., Hou, W., Shields, D., van Pijkeren, J.-P., Mukherjee, A., Epperly, M. W., Vlad, A. M., Coffman, L., Wang, H., Saiful Huq, M., Patel, R., Huang, J., & Greenberger, J. S. (2022). Lactobacillus reuteri Releasing IL-22 (LR-IL-22) Facilitates Intestinal Radioprotection for Whole-Abdomen Irradiation (WAI) of Ovarian Cancer. Radiation Research, 198(1). https://doi.org/10.1667/rade-21-00224.1
Espinal, A., Epperly, M. W., Mukherjee, A., Fisher, R., Shields, D., Wang, H., Huq, M. S., Hamade, D. F., Vlad, A. M., Coffman, L., Buckanovich, R., Yu, J., Leibowitz, B. J., van Pijkeren, J.-P., Patel, R. B., Stolz, D., Watkins, S., Ejaz, A., & Greenberger, J. S. (2022). Intestinal Radiation Protection and Mitigation by Second-Generation Probiotic Lactobacillus-reuteri Engineered to Deliver Interleukin-22. International Journal of Molecular Sciences, 23(10), 5616. https://doi.org/10.3390/ijms23105616
ZHANG, X., FISHER, R., HOU, W., SHIELDS, D., EPPERLY, M. W., WANG, H., WEI, L., LEIBOWITZ, B. J., YU, J., ALEXANDER, L. M., VAN PIJKEREN, J.-P., WATKINS, S., WIPF, P., & GREENBERGER, J. S. (2019). Second-generation Probiotics Producing IL-22 Increase Survival of Mice After Total Body Irradiation. In Vivo, 34(1), 39–50. https://doi.org/10.21873/invivo.11743