C225 antiepidermal growth factor receptor antibody enhances tumor radiocurability

Purpose: Overexpression of epidermal growth factor receptor (EGFR) has been correlated with tumor resistance to radiation. Blockade of EGFR with C225 anti-EGFR antibody was previously shown to synergistically enhance radiatio n-induced tumor growth delay. The purpose of this study was to assess wheth er C225 can increase tumor cure by radiation. Methods and Materials: Nude mice bearing 8-mm-diameter A431 tumor xenograft s in the hind leg were treated with C225 antibody, graded single doses of l ocal tumor irradiation, or both. C225 was given i.p. at a dose of I mg/mous e 6 h before irradiation or 6 h before and 3 plus 6 days after irradiation. Tumor cure was the treatment endpoint assessed by the TCD50 assay 120 days after treatment. The onset of recurrences of tumors not cured was also det ermined. Results: C225 antibody increased the antitumor effects of radiation by redu cing TCD50 values and delaying tu-mor recurrences. Tumor radiocurability wa s enhanced by a factor of 1.18 by a single dose and by a factor of 1.92 by three doses of C225. Likewise, the appearance of tumor recurrences was dela yed by a factor of 1.37 by a single dose and by a factor of 2.13 by three d oses of C225. Conclusion: The data presented here demonstrate that C225 can increase tumo r radiocurability and delay the appearance-of recurrences of tumors not cur ed by radiation treatment. (C) 2001 Elsevier Science Inc.