El anticuerpo 7A7: Una nueva herramienta para la evaluación preclínica de terapias antimetastásicas específicas por el receptor del factor de crecimiento epidérmico

The epidermal growth factor receptor (EGFR) is considered one of the main targets for the treatment of epithelial tumors. Growing evidence shows the essential role of this receptor in disseminating metastasis. The Center of Molecular Immunology (CIM) has pioneered the development of this new therapeutic concept, generating different anti-EGFR agents that are currently under preclinical and clinical evaluation. One of these agents is the h-R3 monoclonal antibody (MAb h-R3), used to treat patients with metastatic tumors. The mechanisms by which the anti-EGFR MAbs exert their anti-metastatic effect is not yet clear, since studies have been made in athymic mice transplanted with human tumors, where the role of T cells cannot be characterized. We obtained here for the first time a MAb that can recognize the extracellular domain of the murine EGFR, named 7A7. It allowed us to confirm the potent anti-metastatic effect of anti-EGFR MAbs in immunocompetent mice. The EGFR signaling inhibition, mediated by anti-proliferative, anti-migratory and pro-apoptotic effects contributes to its anti-metastatic effect. Also, these results suggest the induction of cytotoxic responses through the Fc region of 7A7 could increase its antitumor effect. This was also the first report of a MAb that depends on CD4⁺ and CD8⁺ T cell functions to exert its anti-metastatic effects.