| Targeting cell surface β2 -microglobulin by pentameric IgM antibodies. | |
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MedLine Citation:
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PMID: 21554263 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Monoclonal antibodies (mAbs) specific for human β(2) -microglobulin (β(2) M) have been shown to induce tumour cell apoptosis in haematological and solid tumours via recruiting major histocompatibility complex (MHC) class I molecules into and excluding cytokine receptors from the lipid rafts. Based on these findings, we hypothesized that IgM anti-β(2) M mAbs might have stronger apoptotic effects because of their pentameric structure. Our results showed that, compared with IgG mAbs, IgM anti-β(2) M mAbs exhibited stronger tumouricidal activity in vitro against different tumour cells, including myeloma, mantle cell lymphoma, and prostate cancer, and in vivo in a human-like xenografted myeloma mouse model without damaging normal tissues. IgM mAb-induced apoptosis is dependent on the pentameric structure of the mAbs. Disrupting pentameric IgM into monomeric IgM significantly reduced their ability to induce cell apoptosis. Monomeric IgM mAbs were less efficient at recruiting MHC class I molecules into and exclusion of cytokine receptors from lipid rafts, and at activating the intrinsic apoptosis cascade. Thus, we developed and validated the efficacy of anti-β(2) M IgM mAbs that may be utilized in the clinical setting and showed that IgM anti-β(2) M mAbs may be more potent than IgG mAbs at inducing tumour apoptosis. |
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Authors:
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Yabing Cao; Yongsheng Lan; Jianfei Qian; Yuhuan Zheng; Sungyoul Hong; Haiyan Li; Michael Wang; Larry W Kwak; Dongyu Lin; Jing Yang; Qing Yi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-05-09 |
Journal Detail:
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Title: British journal of haematology Volume: 154 ISSN: 1365-2141 ISO Abbreviation: Br. J. Haematol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-09 Completed Date: 2011-08-30 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 111-21 Citation Subset: IM |
Copyright Information:
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© 2011 Blackwell Publishing Ltd. |
Affiliation:
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Department of Lymphoma/Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / immunology*, therapeutic use Apoptosis / immunology Dose-Response Relationship, Immunologic Histocompatibility Antigens Class I / metabolism Humans Immunoglobulin M / immunology*, therapeutic use Membrane Microdomains / metabolism Mice Mice, Inbred NOD Mice, SCID Molecular Targeted Therapy / methods Multiple Myeloma / immunology, pathology*, therapy Receptors, Interleukin-6 / metabolism Tumor Cells, Cultured Xenograft Model Antitumor Assays beta 2-Microglobulin / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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K99/R00 CA137158/CA/NCI NIH HHS; P50 CA142509/CA/NCI NIH HHS; R01 CA138398/CA/NCI NIH HHS; R01 CA138398-01A2/CA/NCI NIH HHS; R01 CA138402/CA/NCI NIH HHS; R01 CA138402-01/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Histocompatibility Antigens Class I; 0/Immunoglobulin M; 0/Receptors, Interleukin-6; 0/beta 2-Microglobulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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