Engineered lisyl oxidase lipid-based nanovesicles for the treatment of solid tumors: on the path to clinical application TRUST

30% of breast cancer patients and 40% of sarcoma patients will develop metastases representing the leading cause of death for these diseases. The 5-years survival rate is 33% for metastatic breast cancer and 15% for advanced sarcoma patients. For metastatic disease standard first-line agents, anthracyclines or taxanes, are not always effective and suffer from systemic toxicity. For localized sarcoma radical surgery is the current standard of care combined with (neo)adjuvant treatments in selected cases. In the metastatic setting chemotherapy is the gold standard but outcomes are still very limited. Thus there is a pressing clinical need to improve patient outcomes and reduce chemotherapy systemic toxicity. Targeting the tumor microenvironment proteins is an option to accumulate chemotherapeutics to the tumor site and in this context the ECM-associated enzymes lysyl oxidase (LOX) family, are promising candidates since they are overexpressed in both primary and metastatic lesions of tumors including breast cancer and sarcomas. Lipid-based vesicles functionalized with a LOX antibody (LIPO-LOX) loaded with anthracycline chemotherapy have been shown to be effective for the treatment of TNBC. Starting from these premises, TRUST proposes to improve TNBC and sarcoma treatments using LIPO-LOX drug delivery systems where antibodies are bioconjugated on liposomes surface in an oriented manner. This project will develop a strategy based on a cutting edge approach for treating solid tumors based on personalized therapeutic strategies and will plan tailored clinical trials using this innovative therapeutic agents.