Targeting of EpCAM using DARPin molecules for theranostics of ovarian cancer

Efficient treatment of disseminated ovarian cancer (OC) remains an unmet clinical need.

Targeted delivery of cytotoxic payload (drugs or toxins) selectively to tumor cells while sparing healthy tissues might improve efficacy and safety.

The goal of the proposed research is to investigate the feasibility of using designed ankyrin repeat protein (DARPin) for targeting epithelial cell adhesion molecule (EpCAM) in ovarian cancer.

I will apply the principles of personalized medicine for the development of diagnostic and therapeutic (theranostic) agents.

Precise conjugation of payload to DARPin would provide uniform therapeutic agents with well-defined pharmacokinetics and toxicity profile. Radiolabeling will be used to characterize the conjugates in vitro and quantify their biodistribution in vivo.

At the first stage of the project (2-years 3 months), the molecular design of DARPin-based targeting cytotoxic constructs, cytotoxicity, biodistribution profile and tumor-targeted delivery in vivo will be invetigated. At the second stage (1-year) the feasibility of experimental cancer therapy will be investigated.

The third stage (9 months) is aimed to investigate factors influencing the contrast of radionuclide imaging of EpCAM, such as radiolabeling chemistry.

This project will provide important information about structure-property relationship and pharmacokinetic profile of a novel class of targeting agents for development of more effective and safer therapies of cancer.