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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Friedman, Lilach M. Schechter, Bilha Lyass, Ljuba Rinon, Ariel Sela, Michael Yarden, Yosef Bacus, Sarah S. Lavi, Sara |
| Description | Author Affiliation: Friedman LM ( Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.); |
| Abstract | mAbs to receptor tyrosine kinases such as EGF receptor/ErbB-1 and HER2/ErbB-2 inhibit the tumorigenic growth of certain cancer cells, but although recombinant versions of such Abs are already used in oncology wards, the mechanism underlying immunotherapy remains unknown. We report that anti-EGF receptor Abs promote a slow endocytic process distinct from the rapid EGF-induced receptor internalization. Combining mAbs that engage distinct epitopes significantly accelerates receptor degradation. In addition, mAb combinations are more effective than single Abs in inhibiting HER2 signaling in vitro and tumorigenesis in animals. We present a model attributing efficacy of immunotherapy to the size of Ab-receptor lattices formed at the cell surface, which dictates the rate of endocytic clearance and extent of signaling blockade. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Antibodies, Monoclonal Metabolism Down-Regulation Immunotherapy Neoplasms Therapy Receptor Protein-Tyrosine Kinases Receptor, Epidermal Growth Factor Animals Dynamins Endocytosis Physiology Epitopes Genes, Reporter Mice Mice, Nude Neoplasm Transplantation Immunology Signal Transduction Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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