EphB2 as a therapeutic antibody drug target for the treatment of colorectal cancer
Autor: | Clarissa Chui, Elizabeth Luis, Craig Crowley, Sarajane Ross, Hartmut Koeppen, Christine Tan, Johnny Silva, Paul Polakis, Gretchen Franz, Weiguang Mao, Peter D. Senter |
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Rok vydání: | 2004 |
Předmět: |
Cancer Research
medicine.drug_class Receptor EphB2 Mice Nude Adenocarcinoma Monoclonal antibody Receptor tyrosine kinase Mice Cell Line Tumor medicine Ephrin Animals Humans biology business.industry Immunotoxins Autophosphorylation Antibodies Monoclonal Xenograft Model Antitumor Assays Immunoconjugate Cell killing Oncology Immunology Cancer cell Colonic Neoplasms Cancer research biology.protein Female Antibody business |
Zdroj: | Cancer research. 64(3) |
ISSN: | 0008-5472 |
Popis: | Analysis of human colorectal cancer specimens revealed overexpression of the EphB2 receptor tyrosine kinase. Monoclonal antibodies (MAbs) to extracellular sequence of EphB2 were raised and tested for activity against colorectal cancer cells. One of the MAbs, 2H9, effectively blocked the interaction of ephB2 with ephrin ligands and inhibited the resulting autophosphorylation of the receptor. However, this antibody did not affect the proliferation of cancer cells expressing ephB2. Immunocytochemical analysis revealed rapid internalization of the MAb 2H9 on binding ephB2, suggesting that target-dependent cell killing could be achieved with an antibody-drug conjugate. When MAb 2H9 was conjugated to monomethylauristatin E through a cathepsin B-cleavable linker, it specifically killed ephB2-expressing cancer cells in vitro and in vivo. Our results suggest that ephB2 is an attractive target for immunoconjugate cancer therapy. |
Databáze: | OpenAIRE |
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