The anti-tumor activity of the 7A7 antibody, specific to murine EGFR, is independent of target expression levels in immunocompetent mice

The epidermal growth factor receptor (EGFR), a molecule that is highly expressed in epithelial tumors, provides a clinically validated target for anti-cancer drug development. Anti-EGFR passive agents have shown anti-tumor activity in pre-clinical and clinical trials; optimization of these therapies is currently under active research. So far, no clear association between EGFR expression levels in the tumors and response to EGFR targeting agents has been found. One possible reason could be the lack of appropriate pre-clinical models. Therefore we explored, for the first time, a possible correlation between EGFR expression and the sensitivity to anti-EGFR monoclonal antibody (Mab) treatment, using murine tumors in normal syngeneic hosts and a specific antibody to murine EGFR (7A7 Mab). Two murine lung tumors (TC-1 and 3LL-D122), with equivalent EGFR expression levels, showed different sensitivities to 7A7 Mab treatment although similar reductions in EGFR activation in both cell lines were observed. TC-1 cells were indifferent to complement-dependent cytotoxicity (CDC) mediated by 7A7 Mab. These findings demonstrate that the effectiveness of anti-EGFR Mabs is not exclusively dependent of the EGFR expression in the tumors, suggesting that the escape to the complement cascade could represent a mechanism of resistance to anti-EGFR Mab therapy.