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A Study in an Orthotopic Nude Mouse Model of Squamous Cell Carcinoma of the Oral Tongue

Daisuke Sano, MD, PhD; Sungweon Choi, DDS, PhD; Zvonimir Luka Milas, MD; Ge Zhou, PhD; Chad E. Galer, MD; Ying-Wen Su, MD; Maria Gule, MD; Mei Zhao, MD; Zhenping Zhu, PhD; Jeffrey N. Myers, MD, PhD

Arch Otolaryngol Head Neck Surg. 2009;135(4):411-420.

Objective  To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the vascular endothelial growth factor receptor (DC101) and the epidermal growth factor receptor (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of the oral tongue (SCCOT).

Design  In vivo study.

Setting  A translational research laboratory at a comprehensive cancer center.

Subjects  Male athymic nude mice aged 8 to 12 weeks.

Intervention  To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase (Luc)-expressing OSC-19-Luc and JMAR-Luc cells were injected into the tongues of nude mice. Animals were randomly divided into 4 groups: DC101 alone, cetuximab alone, DC101 plus cetuximab, or placebo, and all treatments were administered twice per week for 4 weeks. The in vivo antitumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunofluorescent staining were performed.

Main Outcome Measures  Tumor size, bioluminescence, animal survival, and percentage of animals with lymph node metastasis.

Results  At the conclusion of the treatment period, the mean tumor volumes in the cetuximab alone and the DC101 plus cetuximab groups had decreased significantly compared with those that received the placebo control (68% [P = .002] and 84% [P < .001], respectively). Significant effects of the treatment were also observed in bioluminescence imaging. Mice treated with DC101 plus cetuximab also lived longer and had a lower incidence of neck lymph node metastases compared with the control group (P = .003).

Conclusions  Treatment with DC101 plus cetuximab inhibited the growth of SCCOT and decreased the incidence of the neck lymph node metastases in vivo. These results suggest that this combination treatment may be an effective strategy against metastatic SCCOT and warrants further preclinical trials.

Author Affiliations: Departments of Head and Neck Surgery (Drs Sano, Choi, Milas, Zhou, Galer, Su, Gule, Zhao, and Myers) and Cancer Biology (Dr Myers), The University of Texas M. D. Anderson Cancer Center, Houston; and ImClone Systems Inc, New York, New York (Dr Zhu).

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