In this report, we examine the interaction between panitumumab, a fully human anti-EGFR monoclonal antibody, and radiation in head and neck squamous cell carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cell lines and xenografts.
Methods and Materials
HNSCC lines UM-SCC-1 and SCC-1483 as well as the NSCLC line H226 were studied. Tumor xenografts in athymic nude mice were utilized to assess the in vivo activity of panitumumab alone and in combination with radiation. In vitro assays were performed to assess the impact of panitumumab on radiation-induced cell signaling, apoptosis, and DNA damage.
Panitumumab increased radiosensitivity as measured by clonogenic survival assay. Radiation-induced EGFR phosphorylation and downstream signaling through MAPK and STAT3 was inhibited by panitumumab. Panitumumab augmented radiationinduced DNA damage by 1.2–1.6-fold in each of the cell lines studied as assessed by residual γ-H2AX foci after radiation. Radiation-induced apoptosis was increased 1.4–1.9-fold by panitumumab, as evidenced by Annexin V-FITC staining and flow cytometry. In vivo, combination therapy with panitumumab and radiation was superior to panitumumab or radiation alone in H226 xenografts (p=0.01) and showed a similar trend in SCC-1483 xenografts (p=0.08). These in vivo findings correlated with immunohistochemistry examination of PCNA; panitumumab with radiation markedly reduced PCNA staining in tumor xenografts.
These studies identify a favorable interaction when combining radiation and panitumumab in upper aerodigestive tract tumor models, both in vitro and in vivo. These data suggest that clinical investigations examining the combination of radiation and panitumumab in the treatment of epithelial tumors warrant further pursuit.