Periodic Reporting for period 1 - PROT-RESIST (Toward the Commercialization of a Proteolytically Resistant APPI Variant for Inhibiting Metastasis in Prostate and Pancreatic Cancer)
Periodo di rendicontazione: 2019-11-01 al 2021-04-30
Distant site tumor metastases are the leading cause of cancer-related deaths, but nonetheless standard-of-care (SoC) treatments and other targeted therapies under development are based on activity against primary tumors rather than on anti-metastatic activity. Our ERC PoC study addressed the specific need for improved anti-metastatic therapies for prostate and pancreatic cancer. In our previous studies we identified mesotrypsin as a promising target for anti-metastatic therapy, and, most importantly, we were able to develop a suitable, i.e. stable and highly selective, inhibitor (namely APPI-3M) for this protease. In our ERC PoC studies, we performed additional modifications to APPI-3M that has led to improved protein stability in serum and decrease the systemic clearance rate from the body. For that, we used two general strategies currently applied to reduce systemic clearance: (i) protein PEGylation or (ii) addition of human serum albumin (HSA) as an element to increase the protein size. These two strategies were explored and allowed us to identify and select the final product for further development. In addition, we were able to show the therapeutic effect of our lead protein APPI-3M in a preclinical breast cancer model. Our pre-clinical development of the stabilized APPI-3M and its commercialization will increase our chances for obtaining a highly efficient and a more affordable therapeutic approach for prostate and breast cancers and potentially for other common cancers.