Human monoclonal antibody fragments binding to insulin-like growth factors I and II with picomolar affinity

UM > Faculty of Health Sciences > DEPARTMENT OF BIOMEDICAL SCIENCES

Status	已發表Published
	Human monoclonal antibody fragments binding to insulin-like growth factors I and II with picomolar affinity
	Zhao, Q.; Feng, Y.; Zhu, Z.; Dimitrov, D.
	2011-09-01
Source Publication	Molecular cancer therapeutics
ISSN	1535-7163
Pages	1677-1685
Abstract	The type 1 insulin-like growth factor receptor (IGF1R) and its ligands (IGF-I and IGF-II) have been implicated in a variety of physiologic processes and in diseases such as cancer. In addition to IGF1R, IGF-II also activates the insulin receptor (IR) isoform A, and therefore, antibodies against IGF-II can inhibit cell proliferation mediated by the signaling through both IGF1R and IR triggered by IGF-II. We identified a new human monoclonal antibody (mAb), m708.2, which is bound to IGF-I and IGF-II but not to insulin. m708.2 potently inhibited signal transduction mediated by the interaction of IGF-I or IGF-II with the IGF1R and IGF-II 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 IGF-I with equilibrium dissociation constant, K(D) = 200 pmol/L and to IGF-II with K(D) = 60 pmol/L. m708.5 inhibited signal transduction mediated by IGF-I and IGF-II 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 IGF-I and IGF-II interactions with IGF1R and IR.
Keyword	monoclonal antibody IGF-I IGF-II
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	55341
Document Type	Journal article
Collection	DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding Author	Dimitrov, D.
Recommended Citation GB/T 7714	Zhao, Q.,Feng, Y.,Zhu, Z.,et al. Human monoclonal antibody fragments binding to insulin-like growth factors I and II with picomolar affinity[J]. Molecular cancer therapeutics, 2011, 1677-1685.
APA	Zhao, Q.., Feng, Y.., Zhu, Z.., & Dimitrov, D. (2011). Human monoclonal antibody fragments binding to insulin-like growth factors I and II with picomolar affinity. Molecular cancer therapeutics, 1677-1685.
MLA	Zhao, Q.,et al."Human monoclonal antibody fragments binding to insulin-like growth factors I and II with picomolar affinity".Molecular cancer therapeutics (2011):1677-1685.

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