Intra-tumor AvidinOX allows efficacy of low dose systemic biotinylated Cetuximab in a model of head and neck cancer

Oncotarget. 2016 Jan 5;7(1):914-28. doi: 10.18632/oncotarget.6089.


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 ( NCT02053324) and present data support its use for the local treatment of HNSCC in combination with systemic administration of low dose bCet.

Keywords: AvidinOX; Cetuximab; HNSCC; bCet; targeted therapy.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Avidin / administration & dosage
  • Biotinylation
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cetuximab / administration & dosage
  • Dose-Response Relationship, Drug
  • ErbB Receptors / metabolism
  • Female
  • Head and Neck Neoplasms / blood supply
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Mice, Nude
  • Neovascularization, Pathologic / prevention & control
  • Treatment Outcome
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays*


  • Antineoplastic Agents
  • Avidin
  • ErbB Receptors
  • Cetuximab

Associated data