Mapping a Tumor-specific Internalizing Epitope Space by Combinatorial Antibody Display

来源 :2005 WHTS3rd Annual Congress of International Drug Discovery | 被引量 : 0次 | 上传用户:hermes262
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  The identification of tumor-specific cell surface antigens is a critical step towards the development of targeted cancer therapeutics.The epitope space at the tumor cell surface is highly complex, composed of proteins, carbohydrate determinants and other post-translational modification products which are difficult to probe solely by gene expression based approaches.This epitope space can be efficiently mapped by complementary monoclonal antibodies.We have used a combinatorial human antibody library as a source of random shape repertoire to directly probe the altered surface chemistry of tumor cells.Selection conditions have been optimized to favor tumor-specific antibody binding and intemalization without prior knowledge of target antigens.We have applied this strategy to the study of prostate cancer,ovarian cancer and mesothelioma, and identified a panel of single chain antibodies that bind to internalizing receptors specifically expressed on the surface of these cancer cells.
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