title: Enhancement of monoclonal antibody efficacy: the effect of external beam radiation.
abstract: External beam irradiation has been shown to enhance accumulation of monoclonal antibodies (MAb) in tumors in vivo. This effect is mainly attributed to an unspecific damage of vascular endothelial cells resulting in an increased vascular leakage. The aim of our studies was to determine the effects of external beam radiation on the expression and function of the epidermal growth factor receptor (EGF-R) in vivo. Expression and internalization of EGF-R was tested in vivo, employing 125I-MAb 425 that binds specifically to the human EGF-R. Irradiation of human high-grade glioma cell lines U87-MG and A1207 with increasing doses (0-3600 Rad) of 240 kVp X-rays, markedly enhanced the binding of 125I-MAb 425 to the cell surface. This effect could only be observed for a few days following irradiation. No correlation of the radiation dose and overexpression of EGF-R were found. At the same time, irradiation stimulated significant and dose-dependent internalization of 125I-MAb. Internalization and intranuclear accumulation of 125I-MAb are necessary to explain the radiocytotoxic effects of 125I. The combination of external beam irradiation and labeled MAb 425 showed at least additive effects on tumor cell survival, when the interval between irradiation and MAb treatment was short. Our data support the clinical observations in the adjuvant treatment of high grade gliomas with 125I-MAb 425 following surgery and external beam radiation.
authors.affiliation: Department of Nuclear Medicine, University of Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bender
authors.forename: J G
authors.initials: JG
authors.lastname: Emrich
authors.forename: J
authors.initials: J
authors.lastname: Eshelman
authors.forename: M A
authors.initials: MA
authors.lastname: Chu
authors.forename: Z
authors.initials: Z
authors.lastname: Steplewski
authors.forename: H J
authors.initials: HJ
authors.lastname: Biersack
authors.forename: L W
authors.initials: LW
authors.lastname: Brady
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000276:immunology / Q000532:radiotherapy*; D002455:Cell Division / Q000276:immunology / Q000528:radiation effects; D002470:Cell Survival / Q000276:immunology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D066246:ErbB Receptors / Q000276:immunology / Q000528:radiation effects; D005910:Glioma / Q000276:immunology / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D018714:Radiotherapy, Adjuvant; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D066246:ErbB Receptors