Combined modality therapy of A431 human epidermoid cancer using anti-EGFr antibody C225 and radiation

Background Monoclonal antibodies (mAb) to epidermal growth factor receptor (EGFr) inhibit tumor cell proliferation and enhance cytotoxicity of chemoth erapeutic agents. The purpose of this study was to investigate the interact ion of the anti-EGFr antibody C225 combined with radiotherapy (RT) on EGFr expressing A431 human epidermoid cancer cells. Methods. Cell proliferation, apoptosis, EGFr expression and phosphorylation, and clonogenic survival we re assayed in vitro. A431 tumor growth inhibition and immunohistochemistry analysis of EGFr expression and apoptosis were assessed in vivo. Results, C 225 plus RT produced greater inhibition of A431 cell proliferation than C22 5 or RT alone which was corroborated by enhanced apoptosis. Similar clonoge nic survival occurred following the addition of C225 to RT, although coloni es were smaller in the presence of C225. C225 produced inhibition of ECF-in duced phosphorylation of EGFr without concurrent down-regulation of surface receptor, which was not altered by RT Combined treatment of mice bearing t umors demonstrated enhancement of complete regressions, reduction in time t o tumor size doubling and prolongation of survival. Significant apoptosis o ccurred in xenograft tumors treated with C225 with or without RT. Conclusio ns. These data demonstrate an interaction between C225 and RT. C225-mediate d apoptosis and inhibition of EGFr phosphorylation may be critical in the i nteraction. Studies to define the precise influence of combined modality tr eatment on the EGFr signal transduction cascade need to be pursued. The com bination of growth factor receptor antibodies and RT has potential applicat ion in clinical oncology.