title: Intra-tumor AvidinOX allows efficacy of low dose systemic biotinylated Cetuximab in a model of head and neck cancer.
abstract: For locally advanced and metastatic head and neck squamous cell carcinoma (HNSCC), the current clinical use of Cetuximab in chemo/radiotherapy protocols is often associated to severe systemic toxicity. Here we report in vitro data in human FaDu pharynx SCC cells, showing that inactive concentrations of biotinylated Cetuximab (bCet) become active upon anchorage to AvidinOX on the surface of tumor cells. AvidinOX-anchored bCet induces apoptosis and DNA damage as well as specific inhibition of signaling, degradation and abrogation of nuclear translocation of EGFR. In the mouse model of FaDu cancer, we show that intra-tumor injection of AvidinOX allows anti-tumor activity of an otherwise inactive, intraperitoneally delivered, low dose bCet. Consistently with in vitro data, in vivo tumor inhibition is associated to induction of apoptosis, DNA damage and reduced angiogenesis. AvidinOX is under clinical investigation for delivering radioactive biotin to inoperable tumors (ClinicalTrials.gov NCT02053324) and present data support its use for the local treatment of HNSCC in combination with systemic administration of low dose bCet.
authors.affiliation: Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Vesci
authors.affiliation: Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy.
authors.forename: Ferdinando Maria
authors.initials: FM
authors.lastname: Milazzo
authors.affiliation: Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Anastasi
authors.affiliation: Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Petronzelli
authors.affiliation: Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Chiapparino
authors.affiliation: Tissue Macro Array Lab, University of Tor Vergata, via della Ricerca Scientifica, 00133, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Carollo
authors.affiliation: Takis Biotech, Castel Romano, 00128, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Roscilli
authors.affiliation: Takis Biotech, Castel Romano, 00128, Rome, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Marra
authors.affiliation: Takis Biotech, Castel Romano, 00128, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Luberto
authors.affiliation: Takis Biotech, Castel Romano, 00128, Rome, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Aurisicchio
authors.affiliation: Takis Biotech, Castel Romano, 00128, Rome, Italy.
authors.forename: Maria Lucrezia
authors.initials: ML
authors.lastname: Pacello
authors.affiliation: Tissue Macro Array Lab, University of Tor Vergata, via della Ricerca Scientifica, 00133, Rome, Italy.
authors.forename: Luigi Giusto
authors.initials: LG
authors.lastname: Spagnoli
authors.affiliation: Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: De Santis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001360:Avidin / Q000008:administration & dosage; D019921:Biotinylation; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001360:Avidin; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: AvidinOX; Cetuximab; HNSCC; bCet; targeted therapy