Immune activation by epidermal growth factor receptor-specific monoclonal antibody therapy for head and neck cancer

Objective: To determine if the epidermal growth factor receptor (EGFR)-specific monoclonal antibodies (mAbs) cetuximab or panitumumab mediate in vitro immune activation against squamous cell carcinoma of the head and neck (SCCHN) cell lines. Design: In vitro study. Setting: Basic science research laboratory. Intervention: Squamous cell carcinoma of the head and neck cell lines were treated with the Food and Drug Administration-approved EGFR-specific mAbs cetuximab or panitumumab in the presence or absence of peripheral blood mononuclear cells from healthy donors. Main Outcome Measures: Cetuximab and panitumumab were compared in terms of their cytotoxic effects, ability to induce apoptosis, bind to EGFR, and block phosphorylation of this receptor in SCCHN cell lines. Results: We demonstrate that both cetuximab and panitumumab have similar levels of EGFR binding, induction of apoptosis, cell lysis, and inhibition of phospho-EGFR in SCCHN cell lines, suggesting similar direct effects. However, neither of these mAbs demonstrated in vitro antitumor activity when used alone. In contrast, in the presence of peripheral blood lymphocytes, either of them can mediate antibody-dependent cell cytotoxicity in vitro when used in doses similar to those found in patients receiving them clinically. Conclusion: We propose that antibody-dependent cell cytotoxicity may constitute an important antitumor mechanism that could contribute to overall clinical effectiveness of EGFR-specific antibodies.