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Human monoclonal antibodies to IGF1/2 with picomolar affinity
Qi Zhao; Yang Feng; Zhongyu Zhu; Dimiter S. Dimitrov
2011
Source PublicationMOLECULAR CANCER THERAPEUTICS
ISSN1535-7163
Volume10Issue:9Pages:1677-1685
Abstract

The type 1 insulin-like growth factor receptor (IGF1R) and its ligands (IGF1 and IGF2) have been implicated in a variety of physiological processes and in diseases such as cancer. In addition to IGF1R, IGF2 also activates the insulin receptor (IR) isoform A and therefore antibodies against IGF2 can inhibit cell proliferation mediated by the signaling through both IGF1R and IR triggered by IGF2. We identified a new human monoclonal antibody (mAb), m708.2, which bound to IGF1 and IGF2 but not to insulin. m708.2 potently inhibited signal transduction mediated by the interaction of IGF1 or IGF2 with the IGF1R and IGF2 with the IR. It also inhibited the growth of the breast cancer cell line MCF-7. An affinity-matured derivative of m708.2, m708.5, bound to IGF1 with equilibrium dissociation constant, KD = 200 pM and to IGF2 with KD = 60 pM. m708.5 inhibited signal transduction mediated by IGF1 and IGF2 and cancer cell growth more potently than m708.2. These results suggest that m708.5 could have potential as a candidate therapeutic for cancers driven by the IGF1,2 interactions with IGF1R and IR.

KeywordMab Igf2 Picomolar Affinity Phage Display Yeast Display Igf1
DOIhttps://doi.org/10.1158/1535-7163.MCT-11-0281
Indexed BySCIE
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000294668900015
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Cited Times [WOS]:30   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorDimiter S. Dimitrov
AffiliationProtein Interactions Group, Center for Cancer Research Nanobiology Program, National Cancer Institute (NCI)-Frederick, National Institutes of Health (NIH), Frederick, MD 21702-1201, USA
Recommended Citation
GB/T 7714
Qi Zhao,Yang Feng,Zhongyu Zhu,et al. Human monoclonal antibodies to IGF1/2 with picomolar affinity[J]. MOLECULAR CANCER THERAPEUTICS,2011,10(9):1677-1685.
APA Qi Zhao,Yang Feng,Zhongyu Zhu,&Dimiter S. Dimitrov.(2011).Human monoclonal antibodies to IGF1/2 with picomolar affinity.MOLECULAR CANCER THERAPEUTICS,10(9),1677-1685.
MLA Qi Zhao,et al."Human monoclonal antibodies to IGF1/2 with picomolar affinity".MOLECULAR CANCER THERAPEUTICS 10.9(2011):1677-1685.
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