THE BIOLOGIC EFFECTS OF C225, A CHIMERIC MONOCLONAL-ANTIBODY TO THE EGFR, ON HUMAN PROSTATE CARCINOMA

For prostate cancer, a correlation exists between overexpression of th e epidermal growth factor receptor (EGFR) and poor clinical prognosis. In addition, late-stage metastatic disease is characterized by a chan ge from a paracrine to an autocrine mode of expression for TGF-alpha, the ligand for the EGFR. These observations suggest that activation of the EGFR may be important for the growth of prostatic carcinoma in si tu, and blockade of the receptor-ligand interaction may offer a means of therapeutic intervention for this disease. We describe the biologic effects of a chimeric anti-EGFR monoclonal antibody, C225, on several human prostate tumor cell lines in culture and the tumor inhibitory p roperties of the antibody for the treatment of human prostate carcinom a xenografts in nude mice. In vitro analysis of the EGFR from androgen -responsive and independent prostatic carcinoma cell lines revealed th at C225 blocked EGF-induced receptor activation and induced internaliz ation of the receptor. In vivo, a treatment regimen of C225 alone or a ntibody plus doxorubicin significantly inhibited tumor progression of well-established DU145 and PC-3 xenografts in nude mice. These results suggest that C225 may have utility for the treatment of human prostat e carcinoma in a clinical setting.