Treatment of pancreatic cancer by combination therapy with oncolytic coxsackie B3 virus PD-H-375TS, focal adhesion kinase inhibitors and checkpoint inhibitors

• Applicants: Dr. Henry Fechner; Professor Dr. Robert Klopfleisch; Professorin Dr. Sophie van Linthout, Ph.D.
• Subject Area: Gastroenterology ; Hematology, Oncology ; Immunology ; Virology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536819681

Pancreatic cancer currently has the lowest survival rate of all cancers. Currently, only 8 out of 100 patients diagnosed with pancreatic cancer survive more than 5 years. Immunotherapies and targeted therapies are among the new treatment concepts on which great hopes are pinned for improving therapeutic success. These include oncolytic viruses, focal adhesion kinase inhibitors (FAKi) and checkpoint inhibitors. In our preliminary work, we have been able to show that the oncolytic coxsackievirus B3 variant PD-H that we developed can infect and destroy pancreatic cancer cell lines in vitro and inhibit the growth of pancreatic tumors in vivo. Furthermore, we could show that in pancreatic cancer cells the proliferation-promoting effect of FAK can be inhibited by an FAKi. The aim of the project is to determine the therapeutic potential of a combination of PD-H-375TS (second generation PD-H), FAKi and checkpoint inhibitors and to elucidate mechanisms contributing to therapeutic success. The studies will be performed in syngeneic pancreatic tumor models with orthotopic pancreas tumors. With our work we hope to contribute to the improvement of therapeutic options in pancreatic cancer.

• DFG Programme: Research Grants