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

TitleCharacterization of a chimeric monoclonal antibody against the insulin-like growth factor-I receptor.
Authors
Issue Date2009
PublisherLandes 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.
Persistent Identifierhttp://hdl.handle.net/10722/91715
ISSN
2013 SCImago Journal Rankings: 1.547
PubMed Central ID
ISI Accession Number ID

 

Author Affiliations
  1. National Cancer Institute at Frederick
DC FieldValueLanguage
dc.contributor.authorZhang, MYen_HK
dc.contributor.authorFeng, Yen_HK
dc.contributor.authorWang, Yen_HK
dc.contributor.authorDimitrov, DSen_HK
dc.date.accessioned2010-09-17T10:24:11Z-
dc.date.available2010-09-17T10:24:11Z-
dc.date.issued2009en_HK
dc.identifier.citationMabs, 2009, v. 1 n. 5, p. 475-480en_HK
dc.identifier.issn1942-0870en_HK
dc.identifier.issn1942-0862en_HK
dc.identifier.urihttp://hdl.handle.net/10722/91715-
dc.description.abstractThe 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.en_HK
dc.languageengen_HK
dc.publisherLandes Bioscience. The Journal's web site is located at http://www.landesbioscience.com/journals/mabs/-
dc.relation.ispartofmAbsen_HK
dc.subject.meshAntibodies, Monoclonal - chemistry - genetics - immunology - metabolism-
dc.subject.meshReceptor, IGF Type 1 - immunology - metabolism-
dc.subject.meshRecombinant Proteins - chemistry - genetics - immunology - metabolism-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.titleCharacterization of a chimeric monoclonal antibody against the insulin-like growth factor-I receptor.en_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1942-0862&volume=1&issue=5&spage=475&epage=480&date=2009&atitle=Characterization+of+a+chimeric+monoclonal+antibody+against+the+insulin-like+growth+factor-i+receptor-
dc.identifier.emailZhang, MY:zhangmy@hku.hken_HK
dc.identifier.authorityZhang, MY=rp01409en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.pmid20065647en_HK
dc.identifier.pmcidPMC2759497-
dc.identifier.scopuseid_2-s2.0-77950358405en_HK
dc.identifier.scopuseid_2-s2.0-77953655319en_HK
dc.identifier.hkuros170373-
dc.identifier.volume1en_HK
dc.identifier.issue5en_HK
dc.identifier.spage475en_HK
dc.identifier.epage480en_HK
dc.identifier.isiWOS:000271989300009-
dc.identifier.scopusauthoridZhang, MY=35316639300en_HK
dc.identifier.scopusauthoridFeng, Y=7404544509en_HK
dc.identifier.scopusauthoridWang, Y=35774687300en_HK
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_HK

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