A novel extracellular drug conjugate significantly inhibits head and neck squamous cell carcinoma

作者：Sweeny Larissa; Hartman Yolanda E; Zinn Kurt R; Prudent James R; Marshall David J; Shekhani Mohammed S; Rosenthal Eben L^*

来源：Oral Oncology, 2013, 49(10): 991-997.

DOI：10.1016/j.oraloncology.2013.07.006

• Aerodigestive squamous cell carcinoma
• Head and neck
• Extracellular drug conjugate
• CD147

Objectives: Despite advances in treatment modalities, head and neck squamous cell carcinoma (HNSCC) remains a challenge to treat with poor survival and high morbidity, necessitating a therapy with greater efficacy. EDC22 is an extracellular drug conjugate of the monoclonal antibody targeting CD147 (glycoprotein highly expressed on HNSCC cells) linked with a small drug molecule inhibitor of Na, K-ATPase. In this study, EDC22%26apos;s potential as a treatment modality for HNSCC was performed. %26lt;br%26gt;Materials and methods: HNSCC cell lines (FADU, OSC-19, Cal27, SCC-1) were cultured in vitro and proliferation and cell viability were assessed following treatment with a range of concentrations of EDC22 (0.25-5.00 mu g/mL). Mice bearing HNSCC xenografts (OSC-19, SCC-1) were treated with either EDC22 (3-10 mg/kg), anti-CD147 monoclonal antibody, cisplatin (1 mg/kg) or radiation therapy (2 Gy/week) monotherapy or in combination. %26lt;br%26gt;Results: In vitro, treatment with minimal concentration of EDC22 (0.25 mu g/mL) significantly decreased cellular proliferation and cell viability (p %26lt; 0.0001). In vivo, systemic treatment with EDC22 significantly decreased primary tumor growth rate in both an orthotopic mouse model (OSC-19) and a flank tumor mouse model (SCC-1) (p %26lt; 0.05). In addition, EDC22 therapy resulted in a greater reduction in tumor growth in vivo compared to radiation monotherapy (p %26lt; 0.05) and a similar reduction in tumor growth compared to cisplatin monotherapy. Combination therapy provided no significant further reduction in tumor growth relative to EDC22 monotherapy. %26lt;br%26gt;Conclusion: EDC22 is a potent inhibitor of HNSCC cell proliferation in vitro and in vivo, warranting further investigations of its clinical potential in the treatment of HNSCC.

• 出版日期2013-10