Development of Infigratinib-eluting Seeds for Localized Treatment of Non-muscle Invasive Bladder Cancer (NMIBC)

• Applicant: Dr. Henning Bahlburg
• Subject Area: Reproductive Medicine, Urology
• Term: from 2023 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 520413928

Non-muscle-invasive bladder cancer (NMIBC) has a high propensity to recur (about 70% within 5 years). Thus, repeated tumor resections under general anasthesia are required, often leading to impaired quality of life in patients. In NMIBC, a high rate of fibroblastgrowth factor receptor mutations (FGFR) have been detected. However, treatment with oral FGFR-inhibitors is accompanied by a high rate of adverse events, leading to treatment discontinuation and impaired quality of life. Prof. Peter Black and associates at the Vancouver Prostate Centre (VPC) at the University of British Columbia in Vancouver, Canada, have developped infigratininb-eluting seeds. Preliminary in-vitro tests have shown a sustainable drug release for more than 15 days. Furthermore, tumor growth of FGFR-sensitive cells was inhibited. This project aims to validate the in-vitro model in an in-vivo model involving immunodeficient nude-mice. Tumor cells will be inoculated in this xenograft and tumor growth will be monitored. Once tumor size exceeds 100mm², treatment will be initialized. Mice will be randomized in 4 treatment groups (infigratininb-eluting seeds, seeds without infigratinib-coating, free infigratininb and saline solution). Further tumor growth will be measured along with infigratininb concentrations in blood and urine-samples. In a parallel project in cooperation with the Faculty of Biomedical Engineering, biodegradable seeds will be developped. Furthermore a device allowing seed-implantation by flexible cystoscopy will be designed and tested, allowing seed-implantation without general anaesthesia and minimizing adverse events caused by foreign bodies in the bladder. The infigratinib-eluding seeds used in this project have been developped by Prof. Peter Black and associates at the Vancouver Prostate Centre at the University of British Columbia. A reserach project in this institution is a unique opportunity. Further project in cooperation with the Department of Translationa Uro-Oncology at the Ruhr-University Bochum a planned.

• DFG Programme: WBP Fellowship
• International Connection: Canada
• Host: Professor Dr. Peter C. Black