Oncotarget

Research Papers:

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

Loredana Vesci, Ferdinando Maria Milazzo, Anna Maria Anastasi, Fiorella Petronzelli, Caterina Chiapparino, Valeria Carollo, Giuseppe Roscilli, Emanuele Marra, Laura Luberto, Luigi Aurisicchio, Maria Lucrezia Pacello, Luigi Giusto Spagnoli and Rita De Santis _

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Oncotarget. 2016; 7:914-928. https://doi.org/10.18632/oncotarget.6089

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Abstract

Loredana Vesci1,*, Ferdinando Maria Milazzo1,*, Anna Maria Anastasi1, Fiorella Petronzelli1, Caterina Chiapparino1, Valeria Carollo2, Giuseppe Roscilli3, Emanuele Marra3, Laura Luberto3, Luigi Aurisicchio3, Maria Lucrezia Pacello3, Luigi Giusto Spagnoli2, Rita De Santis1

1Biotechnology, Research & Development, Sigma-Tau SpA, 00071 Pomezia, Rome, Italy

2Tissue Macro Array Lab, University of Tor Vergata, via della Ricerca Scientifica, 00133, Rome, Italy

3Takis Biotech, Castel Romano, 00128, Rome, Italy

*These authors have contributed equally to this work

Correspondence to:

Rita De Santis, e-mail: [email protected]

Keywords: HNSCC, AvidinOX, Cetuximab, bCet, targeted therapy

Received: July 07, 2015     Accepted: October 26, 2015     Published: November 07, 2015

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.


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