dc.contributor.author | Hackel, Benjamin J. | |
dc.contributor.author | Neil, Jason Robert | |
dc.contributor.author | White, Forest M. | |
dc.contributor.author | Wittrup, Karl Dane | |
dc.date.accessioned | 2013-07-10T13:50:45Z | |
dc.date.available | 2013-07-10T13:50:45Z | |
dc.date.issued | 2011-12 | |
dc.date.submitted | 2011-09 | |
dc.identifier.issn | 1741-0126 | |
dc.identifier.issn | 1741-0134 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/79433 | |
dc.description.abstract | No single engineered protein has been shown previously to robustly downregulate epidermal growth factor receptor (EGFR), a validated cancer target. A panel of fibronectin-based domains was engineered to bind with picomolar to nanomolar affinity to multiple epitopes of EGFR. Monovalent and homo- and hetero-bivalent dimers of these domains were tested for EGFR downregulation. Selected orientations of non-competitive heterodimers decrease EGFR levels by up to 80% in multiple cell types, without activating receptor signaling. These heterodimers inhibit autophosphorylation, proliferation and migration, and are synergistic with the monoclonal antibody cetuximab in these activities. These small (25 kDa) heterodimers represent a novel modality for modulating surface receptor levels. | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (NIH grant CA96504) | en_US |
dc.description.sponsorship | National Institutes of Health (U.S.) (NIH grant CA118705) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (Graduate Research Fellowship Program) | en_US |
dc.language.iso | en_US | |
dc.publisher | Oxford University Press | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1093/protein/gzr056 | en_US |
dc.rights | Creative Commons Attribution-Noncommercial-Share Alike 3.0 | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/ | en_US |
dc.source | PMC | en_US |
dc.title | Epidermal growth factor receptor downregulation by small heterodimeric binding proteins | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Hackel, B. J., J. R. Neil, F. M. White, and K. D. Wittrup. Epidermal Growth Factor Receptor Downregulation by Small Heterodimeric Binding Proteins. Protein Engineering Design and Selection 25, no. 2 (January 16, 2012): 47-57. | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Biological Engineering | en_US |
dc.contributor.department | Massachusetts Institute of Technology. Department of Chemical Engineering | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Hackel, Benjamin J. | en_US |
dc.contributor.mitauthor | Neil, Jason Robert | en_US |
dc.contributor.mitauthor | White, Forest M. | en_US |
dc.contributor.mitauthor | Wittrup, Karl Dane | en_US |
dc.relation.journal | Protein Engineering Design and Selection | en_US |
dc.eprint.version | Author's final manuscript | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Hackel, B. J.; Neil, J. R.; White, F. M.; Wittrup, K. D. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-1545-1651 | |
dc.identifier.orcid | https://orcid.org/0000-0003-2398-5896 | |
mit.license | OPEN_ACCESS_POLICY | en_US |
mit.metadata.status | Complete | |