Protease‐guided tumor targeting tools to revolutionize cancer diagnosis and treatment.

Europe has a high cancer burden: in 2020, 2.7 million EU citizens were diagnosed with the disease and 1.3 million lost their lives to it. This toll is expected to increase further, mainly because Europe's population is ageing: by 2035, cancer will be the leading cause of death in the EU. In 2021, the EC published its ‘Europe's Beating Cancer Plan’ (EBCP), calling for a big push in cancer research. Cancer diagnostics and therapeutics should rapidly become more effective and selective, patient-friendly and personalized.

All these goals are directly addressed by developing better tumor targeting strategies. Typically, they consist of equipping diagnostics and therapeutics with a vector unit. The vector unit binds to a protein that is overexpressed on cancer cells or in the Tumor Micro-Environment (TME), causing the diagnostic or therapeutic payload to accumulate in the tumor. Over the last decades, huge effort has gone in approaches that use antibodies as vectors, but return-on-investment has overall been rather poor. Exciting, recent innovations rely on small molecule vectors that target TME proteases. Proteases are ideal candidates for tumor targeting: they are often strongly overexpressed in the TME and possess an active site that allows high-affinity anchoring of vectors. Members of this consortium have played a leading role in these developments.

OncoProTools wants to force breakthroughs in cancer diagnosis and therapy by:

1) Exploring innovative venues for protease targeting in CAR T cell therapy.

2) Discovering novel vectors that bind to other TME proteases: cathepsins S, B, L and granzyme B

3) Personalize applications of protease targeting: deliver innovative diagnostics through deeper understanding of TME biology.

At the same time, OncoProTools will deliver a training program that truly captures the MSCA values, to 10 Doctoral Candidates. They will be provided with all capabilities to become leaders of tomorrow's R&I in Europe.