The Effect of Combination Anti–Endothelial Growth Factor Receptor and Anti–Vascular Endothelial Growth Factor Receptor 2 Targeted Therapy on Lymph Node Metastasis

Abstract

Objective To evaluate the therapeutic effect of treatment with a combination of the monoclonal antibodies to the VEGFR (DC101) and the EGFR (cetuximab) in an orthotopic nude mouse model of metastatic squamous cell carcinoma of oral tongue (SCCOT). Design In vivo study. Subjects 8- to 12- week-old male athymic nude mice. Intervention To develop orthotopic nude mouse models of SCCOT, OSC-19 cells or luciferase-expressing human 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, all given twice per week for 4 weeks. The in vivo anti-tumor activity was monitored noninvasively by bioluminescence imaging. Tumors were resected at necropsy, and immunohistochemical and immunoflourescent staining were performed. Results At the conclusion of the treatment period, the average tumor volumes in the cetuximab alone and the DC101 plus cextuximab treatment groups had decreased significantly compared with those that received control (68%, P=0.002 and 84%, P=0.0003 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=0.003). Conclusion 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 stategy against metastatic SCCOT and warrants further pre-clinical trials.

Orthotopic non-metastatic and metastatic oral cancer mouse models

“…Orthotopic transplantation of tumor cells remains a reproducible and reliable methodology for studying mechanisms and potential therapeutic applications, since phenotypic properties of metastatic cells are governed by the expression of genes that are regulated by interactions with the relevant organ-specific microenvironment [10]. However, these orthotopic OSCC mouse models rely on the use of bioluminescence, which is fraught with transient and variable signals, and they exhibit limited metastasis [11,12] that do not reflect many sites observed in human OSCC [13–17]. …”

Stable gene-silence of Kif2a synergistic with 5-fluorouracil suppresses oral tongue squamous cell carcinoma growth in vitro and in vivo

“…2,3,11 Recently, a targeted molecular therapy has been reported to greatly improve prognoses of this malignant disease, e.g., Cetuximab, a monoclonal antibody of EGFR. 12,13 However, more potential biological targets for the treatment and therapy of SCCOT need to be explored. Previously, we identified that Kif2a, a microtubule motor protein in the Kinesin-13 family, is involved in the progression, invasion and metastasis of SCCOT.…”

Noncovalent Assembly of Targeted Carbon Nanovectors Enables Synergistic Drug and Radiation Cancer Therapy in Vivo

“…29 An orthotopic nude mouse model of oral tongue cancer was established by injecting FaDu (2.5 × 10 5 ) or OSC-19 (5 × 10 4 ) cells suspended in 30 µL of serum-free DMEM into the tongues of mice as described previously. 30 …”