Anti-HER2 radioimmunotherapy.
HER2/neu is a receptor protein whose overexpression strongly correlates with poor prognosis in breast carcinomas. It is used increasingly as a therapeutic target for breast carcinomas in clinical human trials. In particular, monoclonal antibodies (mAbs) that target HER2/neu have been investigated for therapeutic applications. Anti-Her2 mAbs linked to radionuclides have been used in pre-clinical models and in patients for radioimmunolocalization of tumors using external scintigraphy and intraoperative handheld gamma detecting probes. Initial efforts of systemic radioimmunotherapy employed radio-iodinated mAbs. In a murine human breast cancer xenograft model, the radiolabeled mAb was 20-fold more effective than the unarmed mAb but did not yield permanent eradication of the tumor. Due to the limitations of radio-iodine ((131)I), metallic radionuclides (e.g, the beta(-)-emmiter (90)Y or the alpha-emitters (213)Bi, (212)Bi, (212)Pb) linked to mAb's are being evaluated in murine models. Complete elimination of beast cancer xenografts was possible in an adjuvant setting using (212)Pb linked to an anti-HER2/neu mAb. Finally, major efforts are underway to increase the access of the radiolabel to the tumor cell in large solid tumors. One such approach involved a pre-targeting strategy with an initial administration of streptavidin linked to mAb that, after a clearing step, was followed by biotin armed with the radionuclide. Although major challenges must be addressed, HER2/neu represents a very attractive target for systemic radioimmunotherapy of breast cancer.
Brechbiel
M W
MW
Radioimmune and Inorganic Chemistry Section, Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1374, USA.
Waldmann
T A
TA