BIOLOGICAL EFFICACY OF A CHIMERIC ANTIBODY TO THE EPIDERMAL GROWTH-FACTOR RECEPTOR IN A HUMAN TUMOR XENOGRAFT MODEL

The epidermal growth factor receptor (EGFR) is a protein tyrosine kina se expressed on many types of tumor cells, including breast, ovarian, bladder, head and neck, and prostatic carcinoma, There seems to be an association be tween up-regulation of the EGFR and poor clinical progn osis for a number of human cancers, The 225 antibody is a highly speci fic murine monoclonal antibody that binds specifically to the human EG FR with an affinity equal to its ligand, competes with the ligand for binding, and blocks activation of the receptor tyrosine kinase, In add ition, 225 has been shown to inhibit the growth of human tumor xenogra fts in athymic nude mice, The 225 antibody has recently been chimerize d with human IgG1 in its constant region to increase its clinical util ity by decreasing the potential for generation of human antimouse anti bodies in recipients, This report compares the biological effects of 2 25 and its chimeric counterpart (designated C225) against established A431 tumor xenografts in nude mice, The results of these experiments i ndicated that C225 was more effective than 225 in inhibiting tumor gro wth in this model, In addition, many of the animals treated with C225 were tumor free at the end of each treatment protocol, It was determin ed that the dissociation constant of C225 was about 5-fold lower than 225, This suggested that the increased capacity of C225 to compete wit h ligand for binding to the EGFR was responsible for its enhanced in v ivo antitumor effect.