Therapeutic efficacy of intra‑tumor AvidinOX and low systemic dose biotinylated cetuximab, with and without cisplatin, in an orthotopic model of head and neck cancer

Abstract

In a previous study, the efficacy of low intraperitoneal doses of biotinylated cetuximab (bCet) in mice with subcutaneous tumor xenografts of human head and neck cancer (HNC) treated intra-tumors with AvidinOX was reported. Taking into account that the current standard treatment for HNC is the combination of cetuximab and cisplatin, the present study investigated the activity of AvidinOX-targeted bCet with and without cisplatin in an orthotopic model. The results confirmed that administration of intra-tumor AvidinOX makes an otherwise inactive dose of bCet effective in reducing tumor growth, and the addition of a low dose of cisplatin further improved tumor growth inhibition. Supporting the in vivo data, immunohistochemical staining of tumor masses from mice treated with AvidinOX, bCet and cisplatin exhibited the highest tumor cell damage and the lowest angiogenic activity among all treatment groups, measured as the number of γ-H2A.X and cleaved caspase-3-positive cells, and vascular endothelial growth factor-C and platelet and endothelial cell adhesion molecule 1-positive cells, respectively. AvidinOX is currently under clinical investigation to assess its use in delivering radioactive biotin to inoperable tumor lesions (ClinicalTrials. gov: NCT02053324 and NCT03188328). The present study further supported the potential clinical use of AvidinOX to target low bCet doses to inoperable tumor lesions, with or without an additional low dose of cisplatin. Since low doses of highly expensive monoclonal antibodies become effective with AvidinOX and low dose cisplatin, such therapies promise to be cheaper and less toxic than current treatments.

Pretargeting: A Path Forward for Radioimmunotherapy

“…De Santis et al described AvidinOX (Alfasigma S.p.A.), an avidin variant designed to prolong the tissue half-life (2 wk compared with 2 h for native avidin) and to demonstrate cellular and interstitial protein tropism for enhanced PRIT (98). In addition to showing therapeutic promise in preclinical studies (98)(99)(100)(101), AvidinOX PRIT has been studied in clinical investigations (NCT02053324 and NCT03188328, both of which were terminated because of low recruitment).…”