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Targeting Multiple Her-2 Epitopes with Monoclonal Antibodies Results in Improved Antigrowth Activity of a Human Breast Cancer Cell Line in Vitro and in Vivo
Ist Teil von
Clinical cancer research, 2002-06, Vol.8 (6), p.1720-1730
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2002
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
Her-2 (p185 erbB-2 ) is a transmembrane tyrosine kinase receptor, which is encoded by the Her-2/neu proto-oncogene. Her-2 is overexpressed on 30% of highly malignant breast cancers. Monoclonal antibodies (MAbs) against Her-2
inhibit the growth of Her-2-overexpressing tumor cells and this occurs by a variety of mechanisms. One such MAb, Herceptin
(Trastuzumab), has been approved for human use. We have generated a panel of murine anti-Her-2 MAbs against nine different
epitopes on the extracellular domain of Her-2 and have evaluated the antitumor activity of three of these MAbs alone and in
combination, both in vitro and in vivo . We found that MAbs (against different epitopes) make a highly effective mixture, which was more effective than the individual
MAbs in treating s.c. tumor nodules of BT474 cells in SCID mice. In vitro , the MAb mixture was also more effective than the single MAbs in inducing antibody-dependent cellular cytotoxicity and complement-dependent
cytotoxicity, inhibiting cell growth and inducing apoptosis, and inhibiting the secretion of vascular endothelial growth factor.
Taken together, these activities might explain the superior performance of the MAb mixture in vivo .