Biological studies and potential therapeutic applications of monoclonal antibodies and small molecules reactive with theneu/c-erbB-2 protein |
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Authors: | Dougall William C Greene Mark I |
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Institution: | (1) Center for Receptor Biology, Division of Immunology, Room 252 John Morgan Building, 36th and Hamilton Walk, Department of Pathology and Laboratory, Medicine, University of Pennsylvania School of Medicine, 19104 Philadelphia, PA |
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Abstract: | The overexpression of the growth factor receptor p185
neu/c-erbB-2 has been observed in a number of human adenocarcinomas and is mechanistically linked to neoplastic growth. Monoclonal antibodies
raised against extracellular domains of the p185
neu/c-erbB-2 receptor oncoprotein have been utilized to inhibit the pathway ofneu-induced tumor development. Our laboratory has demonstrated a direct effect of anti-p185
neu/c-erbB2 antibodies which requires receptor ligation. This induced aggregation causes the downmodulation of cell-surface expression
and eventual degradation of p185
neu/c-erbB-2 protein. In cells transformed by theneu oncogene, the result of antibody-induced p185
neu/c-erbB-2 receptor modulation is the reversion of the malignant pheno-type. We are exploiting the direct efficacy of this monoclonal
antibody by developing small molecules (peptides and organic mimietics) based on anti-p185
neu/c-erbB-2 antibody structure that can mediate similar receptor binding and biological effects. |
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Keywords: | neu/c-erbB-2 receptor tyrosine kinases monoclonal antibody peptide mimetics tumor therapy |
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