Novel targeted therapy based on dual warhead conjugates against FGFR-dependent cancers
University of Wroclaw ·Poland
About this project
<p>Effective cancer therapy is the most important goal in oncology. The progress in antibody drug conjugates encouraged us to verify if attachment of two different cytotoxins to a targeting protein will lead to a efficient conjugate. The Project stems from our findings that fibroblast growth factor 2 (FGF2) can replace antibody as a targeting protein. FGF2 conjugated with monomethyl auristatin E (MMAE) can destroy cancer cells overexpressing FGF receptor 1. We will produce FGF2 conjugates with two extremely cytotoxic warheads: MMAE and α-amanitin (AMN). Simultaneous application of two drugs is an alternative for conventional combination therapy. MMAE blocks microtubule formation and AMN is RNA polymerase II and III inhibitor. Both warheads should act in concert in a single cancer cell. Further, MMAE can be secreted from cancer cell and via so called bystander effect destroy neighboring cells and AMN shows outstanding activity in cells expressing multi-drug resistant transporters. The most promising dual conjugate will be tested in animal models, including FGFR-dependent xenographs and patient-derived tumor models. The approach is original and addresses trends in anti-cancer drug development: specific delivery, high level of drug loading combined with defined stoichiometry and homogeneiety of conjugate.<br> The consortium of Oslo University Hospital, University of Wroclaw and Pure Biologics represent a team well-suited for the completion of described tasks and will benefit from their diverse background. Proposed tasks are interconnected and we believe that our laboratories are in many aspects highly complementary, providing better chance of successfully delivering project milestones. The project includes both specialized work packages where we can benefit from a deep experience of a consortium partner, along with more interdisciplinary ones, where tight collaboration will enhance knowledge transfer and all the benefits of our previous collaborations will come into play.<br> </p>
Bilateral cooperation results
Within the project we developed the fruitful collaboration between Polish and Norwegian groups, providing platform for exchange of practical laboratory knowledge, experience and ideas, and sharing the results together with experimental methods between project participants. Due to the Polish-Norwegian grant excellent conditions for MS and PhD students were created to develop their scientific skills. Advanced laboratory techniques applied in both laboratories are available for young scientists. PhD students and scientists involved in the project had extraordinary opportunities to attend high quality scientific meetings, conferences and trainings to broaden their knowledge and promote the results obtained within the project. To provide the best cooperation opportunity we organized several visits and meetings, to gather Polish and Norwegian scientists together. All meetings were extremely fruitful and beneficial especially for young PhD students. There were many scientific discussions and exchange of new ideas concerning the project. Knowledge exchange and development were accompanied with social benefits. Working in closely collaborating laboratories located in different countries also influenced the cognition of different cultures and backgrounds. Both Polish and Norwegian partners are willing to continue collaboration between our laboratories. We are going to further exchange the knowhow between laboratories as well as to allow young scientist to learn new technologies during onsite visits.
Project partners
- Oslo University Hospital Donor project partner· Norway
- Pure Biologics S.A. Project partner· Poland