Rita De Santis
Sigma Tau SpA, Italy
Title: AvidinOX-targeted delivery: A new way to improve efficacy of well-known monoclonal antibodies for cancer therapy
Biography
Biography: Rita De Santis
Abstract
We recently discovered that the oxidized version of hen egg white avidin, named AvidinOX, can chemically link to tissue proteins when injected or nebulized, thus becoming an artificial receptor for biotinylated therapeutics. This product is currently under investigation in phase I clinical trials for targeting intravenously administered 177Lutetium-biotinDOTA to inoperable tumor lesions and liver metastases, pre-injected with AvidinOX (ClinicalTrials.gov NCT02053324). Several published and some non-published data from our group indicate that AvidinOX-targeted delivery of the biotinylated version of some marketed monoclonal antibodies turns non-effective doses of such antibodies effective for cancer treatment. Among the antibodies tested, AvidinOX-targeted delivery of biotinylated anti-EGFR cetuximab and panitumumab, and anti-ErbB2/neu trastuzumab and pertuzumab were particularly effective. Molecular mechanisms explaining the improved anti-tumor activity of AvidinOX-anchored biotinylated antibodies have been also described by our group. Overall, our data provide a scientific rational for further pre-clinical and clinical investigation of therapeutic approaches based on the local delivery of AvidinOX (i.e., intra-tumor, aerosol or intra-peritoneal delivery) followed by local or systemic delivery of low dose biotinylated antibodies. The expectation of our AvidinOX-targeted delivery platform is to reduce the cost of cancer treatments and improve tolerability by reaching anti-tumor efficacy with significantly less amount of expensive antibodies.