CEASE cancer: CarcinoEmbryonic Antingen-targeting Scaffold protein Engineering for precision targeted therapy of carcinomas

Affibodies are unconventional targeting proteins, which are based of non-immunoglobulin scaffold and have a number of advantages over antibodies. CEACAM5 is a pancarcinoma antigen, which is overexpressed in many malignancies. An affibody ZCEA:C9 binds to CEACAM5 with high affinity and specificity.

The purpose of the project is to provide scientific rationale for molecular design of ZCEA:C9-based targeting agents for a precision imaging-guided treatment of disseminated cancer by cytotoxic drugs and radionuclides. Factors influencing biodistribution and tumour targeting properties of ZCEA:C9-derivatives will be investigated.

In vitro and in vivo studies concerning structure-property relationship and radionuclide imaging of CEACAM5 expression will be performed in the applicant’s lab at Uppsala University, where relevant methodology is well established.

The production of CEACAM5-binding affibody variants will be performed in collaboration with researches from the TKH-Royal Institute of Technology (Stockholm). Clinical translation is foreseen in Uppsala University Hospital.

The project should be accomplished in 5-years.The applied methodology has been already resulted in development of HER2-targeting affibodies, which are successfully passing Phase I/II clinical studies.

We hope that this project would result in development of agents enabling precision treatment of several disseminated malignancies, including e.g. colorectal, breast, pancreatic, lung and ovarian carcinomas.