CAMNOT Project - CAMelid NanoOnco-Therapeutics – University of Copenhagen

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CAMNOT - CAMelid NanoOnco-Therapeutics

Breast cancer is a major public health problem among women throughout the world and is the second most common cancer that occurs in women. More than 1.1 million cases are diagnosed annually and of these more than 410,000 patients die from breast cancer worldwide.

Denmark has been ranked with having the second highest breast cancer and the highest female and overall cancer rate in the world according to the latest statistics published by the World Cancer Research Fund. The CAMNOT Programme integrates two complimentary advanced biotechnology and bionano-technology research areas between the Nanomedicine Group at UCPH and Biomedical Engineering Group at DTU for a mechanistic approach towards precision nanoengineering and development of highly effective libraries of particulate nanomedicine for diagnosis and treatment of HER2+ breast cancer.

Breast cancer is a heterogeneous disease where 20−30% of cases shows over-expression of the human epidermal growth factor receptor 2 (HER2). Cardiotoxicity and resistance are two frequently encountered complications in HER2+ breast cancer patients receiving Herceptin, which is the only clinically approved anti-HER2 humanized monoclonal antibody. CAMNOT addresses these complications through design of novel anti-cancer nanoparticles functionalized with high affinity variable domain of heavy chain camelid non-conventional antibodies, VHH, (Figure) against HER2.

Because of their small size (~15kDa), general robustness and no need for humanization, these antibody domains are ideal candidates for development of highly effective anti-cancer nanomedicine, and overcome many problems associated with conventional antibodies and their related fragments. The availability of different clones of anti-HER2 VHHs, where each clone exhibit different epitope binding specificity for the extracellular domain of the HER2 antigen, addresses disease heterogeneity, increases versatility in nanomedicine engineering, improves target binding and therapeutic efficacy (multivalancy), and lays the foundation for personalization protocols in breast cancer diagnosis and therapy.

Our success could open the path towards future oligoclonal VHH approaches for population and personalized based mapping and therapeutic interventions for HER2-related breast cancer.