Experimental evidences supporting the epidermal growth factor receptor (EGFR) as an important molecule for tumor metastasis had been accumulated. Currently, anti-EGFR monoclonal antibodies (mAbs) constitute a promising approach for the treatment of patients with metastatic tumors. However, the mechanisms associated with the potent anti-metastatic effect of these mAbs have not been completely elucidated due to the lack of appropriate syngeneic preclinical models. In this paper, we have investigated the effects of 7A7, an antibody specific to murine EGFR, on the metastatic properties of D122 murine lung carcinoma. 7A7 mAb significantly impaired metastatic spread of D122 cells in C57BL/6 mice by direct anti-proliferative and pro-apoptotic effects on tumor metastasis. 7A7 mAb capacity to inhibit EGFR activation on D122 cells could contribute to its anti-metastatic effect. In addition, 7A7 mAb was able to induce in vitro antibody-dependent cell-mediated cytotoxicity on D122 cells. Interestingly, 7A7 mAb treatment increased the number of natural killer cells, T lymphocytes and dendritic cells infiltrating the metastatic sites. More strikingly, depletion of CD8(+) and CD4(+) T cells in vivo completely abrogated the 7A7 mAb anti-metastatic activity whereas function of natural killer cells was irrelevant. This study supports an in vivo role for T cell response in the mechanism of action of anti-EGFR mAbs, suggesting the induction of an adjuvant effect.

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The epidermal growth factor receptor (EGFR) is highly expressed in many types of epithelial tumors. EGFR overexpression has been associated with an advanced stage of the disease, with resistance to standard therapies, and, for certain tumors, with poor patient prognosis. As a result, EGFR has been considered a meaningful target in anti-tumor strategies. Active and passive immunotherapies blocking EGFR and its ligands have been explored. But for successful pre-clinical evaluation of these approaches, well-established murine tumor models are not available and highly desirable. We described, for the first time, the generation and characterization of an anti-murine EGFR extracellular domain monoclonal antibody (7A7 MAb) (IgG1). 7A7 was generated by immunization of Balb/c mice with the recombinant extracellular domain of murine EGFR (rECD-mEGFR). 7A7 recognized an epitope present in the amino acidic core of the antigen and is cross-reactive with the human EGFR. Interestingly, this MAb was able to specifically bind EGFR at the cell surface, allowing the assessment of its differential expression in a panel of murine cells. Noteworthy, in a preliminary immunohistochemical study with 7A7 MAb, recognition of Balb/c mice skin sections and EGFR-positive tumors were observed. We concluded that 7A7 MAb is a valuable tool for EGFR-based therapeutic pre-clinical studies.

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