Article: Characterization of a chimeric monoclonal antibody against the insulin-like growth factor-I receptor.

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Title	Characterization of a chimeric monoclonal antibody against the insulin-like growth factor-I receptor.
Authors	Zhang, MY Feng, Y Wang, Y Dimitrov, DS
Issue Date	2009
Publisher	Landes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/
Citation	Mabs, 2009, v. 1 n. 5, p. 475-480 [How to Cite?]
Abstract	The insulin-like growth factors (IGFs) signaling system has been shown to play important roles in neoplasia. The IGF receptor type 1 (IGF-IR) is overexpressed in many types of solid and hematopoietic malignancies, and there is substantial experimental and clinical evidence that targeting IGF-IR is a promising therapeutic strategy against cancer. It has been previously reported that a mouse monoclonal antibody (mAb), 4G11, blocked IGF-I binding to IGF-IR and downregulated the IGF-IR in MCF-7 cells. We cloned this antibody, constructed a human-mouse chimeric antibody, designated m590, and characterized it. The chimeric IgG1 m590 bound to cell-associated IGF-IR on NWT c43 stably transfected cells and MCF-7 breast cancer cells as efficiently as the parental murine antibody. Using purified IGF-IR extracellular domains, we found that both the chimeric m590 and the parental 4G11 antibodies bind to conformational epitopes on IGF-IR. Neither of these antibodies bound to the insulin receptor (IR) ectodomain. Furthermore, IgG1 m590 blocked the binding of IGF-I and IGF-II to IGF-IR, and inhibited both IGF-I and IGF-II induced phosphorylation of IGF-IR in MCF-7 cells. These results suggest that m590 could be an useful antibody in diagnosis and treatment of cancer, as well as a research tool.
ISSN	1942-0870 1942-0862 2011 Impact Factor: 3.174
ISI Accession Number ID	WOS:000271989300009
PubMed Central ID	PMC2759497

DC Field	Value
dc.contributor.author	Zhang, MY
dc.contributor.author	Feng, Y
dc.contributor.author	Wang, Y
dc.contributor.author	Dimitrov, DS
dc.date.accessioned	2010-09-17T10:24:11Z
dc.date.available	2010-09-17T10:24:11Z
dc.date.issued	2009
dc.description.abstract	The insulin-like growth factors (IGFs) signaling system has been shown to play important roles in neoplasia. The IGF receptor type 1 (IGF-IR) is overexpressed in many types of solid and hematopoietic malignancies, and there is substantial experimental and clinical evidence that targeting IGF-IR is a promising therapeutic strategy against cancer. It has been previously reported that a mouse monoclonal antibody (mAb), 4G11, blocked IGF-I binding to IGF-IR and downregulated the IGF-IR in MCF-7 cells. We cloned this antibody, constructed a human-mouse chimeric antibody, designated m590, and characterized it. The chimeric IgG1 m590 bound to cell-associated IGF-IR on NWT c43 stably transfected cells and MCF-7 breast cancer cells as efficiently as the parental murine antibody. Using purified IGF-IR extracellular domains, we found that both the chimeric m590 and the parental 4G11 antibodies bind to conformational epitopes on IGF-IR. Neither of these antibodies bound to the insulin receptor (IR) ectodomain. Furthermore, IgG1 m590 blocked the binding of IGF-I and IGF-II to IGF-IR, and inhibited both IGF-I and IGF-II induced phosphorylation of IGF-IR in MCF-7 cells. These results suggest that m590 could be an useful antibody in diagnosis and treatment of cancer, as well as a research tool.
dc.description.nature	link_to_OA_fulltext
dc.identifier.citation	Mabs, 2009, v. 1 n. 5, p. 475-480 [How to Cite?]
dc.identifier.epage	480
dc.identifier.hkuros	170373
dc.identifier.isi	WOS:000271989300009
dc.identifier.issn	1942-0870
dc.identifier.issn	1942-0862 2011 Impact Factor: 3.174
dc.identifier.issue	5
dc.identifier.openurl
dc.identifier.pmcid	PMC2759497
dc.identifier.pmid	20065647
dc.identifier.scopus	eid_2-s2.0-77950358405
dc.identifier.scopus	eid_2-s2.0-77953655319
dc.identifier.spage	475
dc.identifier.uri	http://hdl.handle.net/10722/91715
dc.identifier.volume	1
dc.language	eng
dc.publisher	Landes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/
dc.relation.ispartof	mAbs
dc.subject.mesh	Antibodies, Monoclonal - chemistry - genetics - immunology - metabolism
dc.subject.mesh	Receptor, IGF Type 1 - immunology - metabolism
dc.subject.mesh	Recombinant Proteins - chemistry - genetics - immunology - metabolism
dc.subject.mesh	Amino Acid Sequence
dc.subject.mesh	Animals
dc.title	Characterization of a chimeric monoclonal antibody against the insulin-like growth factor-I receptor.
dc.type	Article

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Author Affiliations

National Cancer Institute at Frederick