Growth inhibition of myeloma cells by anti‐idiotype antibodies in the absence of membrane‐bound immunoglobulin
Immunoglobulins are expressed as membrane‐bound or secreted forms. Plasma cells produce little or no membrane immunoglobulin but secrete immunoglobulin molecules in large amounts. Immunoglobulin idiotypes of malignant B cells are tumor‐specific antigens that may be targeted for immunotherapy. Thus,...
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description | Immunoglobulins are expressed as membrane‐bound or secreted forms. Plasma cells produce little or no membrane immunoglobulin but secrete immunoglobulin molecules in large amounts. Immunoglobulin idiotypes of malignant B cells are tumor‐specific antigens that may be targeted for immunotherapy. Thus, idiotype vaccination is being evaluated in clinical trials to control residual disease in multiple myeloma and non‐Hodgkin's lymphoma. It is traditionally considered that anti‐idiotype antibodies are not effective against plasma cell tumors, because the large amounts of immunoglobulin molecules secreted by the tumors block anti‐idiotype antibodies, and because the absence of membrane immunoglobulin on the surface of these tumor cells renders them resistant to the effect of anti‐idiotype antibodies. While the obstacle of abundant circulating idiotype may be obviated by reducing tumor burden to minimal residual disease, the absence of membrane immunoglobulin has been considered as a limiting factor that prevents tumor eradication by anti‐idiotype antibodies. We demonstrate here that murine plasmacytoma cells can produce small amounts of membrane immunoglobulin M (IgM) heavy chains. However, the latter are precursor molecules that do not reach the cell surface. Although membrane‐bound IgM is absent, the cells stain positively for surface IgM, reflecting molecules of the secreted form in the process of secretion. In spite of the relatively low levels of secreted immunoglobulin on the cell surface, anti‐idiotype antibodies are effective in retardation of tumor growth in vivo. Thus, while there is no doubt that idiotype‐specific cell‐mediated responses are very important, myeloma patients in complete remission may additionally benefit from idiotype‐specific humoral responses. |
doi_str_mv | 10.1038/sj.icb.7100153 |
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Plasma cells produce little or no membrane immunoglobulin but secrete immunoglobulin molecules in large amounts. Immunoglobulin idiotypes of malignant B cells are tumor‐specific antigens that may be targeted for immunotherapy. Thus, idiotype vaccination is being evaluated in clinical trials to control residual disease in multiple myeloma and non‐Hodgkin's lymphoma. It is traditionally considered that anti‐idiotype antibodies are not effective against plasma cell tumors, because the large amounts of immunoglobulin molecules secreted by the tumors block anti‐idiotype antibodies, and because the absence of membrane immunoglobulin on the surface of these tumor cells renders them resistant to the effect of anti‐idiotype antibodies. While the obstacle of abundant circulating idiotype may be obviated by reducing tumor burden to minimal residual disease, the absence of membrane immunoglobulin has been considered as a limiting factor that prevents tumor eradication by anti‐idiotype antibodies. We demonstrate here that murine plasmacytoma cells can produce small amounts of membrane immunoglobulin M (IgM) heavy chains. However, the latter are precursor molecules that do not reach the cell surface. Although membrane‐bound IgM is absent, the cells stain positively for surface IgM, reflecting molecules of the secreted form in the process of secretion. In spite of the relatively low levels of secreted immunoglobulin on the cell surface, anti‐idiotype antibodies are effective in retardation of tumor growth in vivo. Thus, while there is no doubt that idiotype‐specific cell‐mediated responses are very important, myeloma patients in complete remission may additionally benefit from idiotype‐specific humoral responses.</description><identifier>ISSN: 0818-9641</identifier><identifier>EISSN: 1440-1711</identifier><identifier>DOI: 10.1038/sj.icb.7100153</identifier><identifier>PMID: 18195726</identifier><language>eng</language><publisher>United States: Nature Publishing Group</publisher><subject>Animals ; Antibodies, Anti-Idiotypic - immunology ; Antibodies, Anti-Idiotypic - therapeutic use ; Antibody-Dependent Cell Cytotoxicity ; B cells ; Cancer Vaccines ; Cell Line, Tumor ; Cell Proliferation - drug effects ; idiotypes ; Immunization, Passive ; immunoglobulin ; Immunoglobulin Idiotypes - biosynthesis ; Immunoglobulin Idiotypes - immunology ; Immunoglobulin M - biosynthesis ; Immunoglobulin M - immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Multiple Myeloma - immunology ; Multiple Myeloma - pathology ; Multiple Myeloma - therapy ; myeloma ; Neoplasm Transplantation ; Receptors, Antigen, B-Cell - deficiency ; Receptors, Antigen, B-Cell - immunology ; vaccination</subject><ispartof>Immunology and cell biology, 2008-03, Vol.86 (3), p.261-267</ispartof><rights>2008 Australasian Society for Immunology Inc.</rights><rights>Copyright Nature Publishing Group Mar 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4003-21d6c9df35e5d9c55836ef01a29b986da9a8866c4c1bacec2d838b0980923a3</citedby><cites>FETCH-LOGICAL-c4003-21d6c9df35e5d9c55836ef01a29b986da9a8866c4c1bacec2d838b0980923a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Fsj.icb.7100153$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Fsj.icb.7100153$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18195726$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moshitzky, Shiri</creatorcontrib><creatorcontrib>Kukulansky, Tova</creatorcontrib><creatorcontrib>Haimovich, Joseph</creatorcontrib><creatorcontrib>Hollander, Nurit</creatorcontrib><title>Growth inhibition of myeloma cells by anti‐idiotype antibodies in the absence of membrane‐bound immunoglobulin</title><title>Immunology and cell biology</title><addtitle>Immunol Cell Biol</addtitle><description>Immunoglobulins are expressed as membrane‐bound or secreted forms. Plasma cells produce little or no membrane immunoglobulin but secrete immunoglobulin molecules in large amounts. Immunoglobulin idiotypes of malignant B cells are tumor‐specific antigens that may be targeted for immunotherapy. Thus, idiotype vaccination is being evaluated in clinical trials to control residual disease in multiple myeloma and non‐Hodgkin's lymphoma. It is traditionally considered that anti‐idiotype antibodies are not effective against plasma cell tumors, because the large amounts of immunoglobulin molecules secreted by the tumors block anti‐idiotype antibodies, and because the absence of membrane immunoglobulin on the surface of these tumor cells renders them resistant to the effect of anti‐idiotype antibodies. While the obstacle of abundant circulating idiotype may be obviated by reducing tumor burden to minimal residual disease, the absence of membrane immunoglobulin has been considered as a limiting factor that prevents tumor eradication by anti‐idiotype antibodies. We demonstrate here that murine plasmacytoma cells can produce small amounts of membrane immunoglobulin M (IgM) heavy chains. However, the latter are precursor molecules that do not reach the cell surface. Although membrane‐bound IgM is absent, the cells stain positively for surface IgM, reflecting molecules of the secreted form in the process of secretion. In spite of the relatively low levels of secreted immunoglobulin on the cell surface, anti‐idiotype antibodies are effective in retardation of tumor growth in vivo. Thus, while there is no doubt that idiotype‐specific cell‐mediated responses are very important, myeloma patients in complete remission may additionally benefit from idiotype‐specific humoral responses.</description><subject>Animals</subject><subject>Antibodies, Anti-Idiotypic - immunology</subject><subject>Antibodies, Anti-Idiotypic - therapeutic use</subject><subject>Antibody-Dependent Cell Cytotoxicity</subject><subject>B cells</subject><subject>Cancer Vaccines</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>idiotypes</subject><subject>Immunization, Passive</subject><subject>immunoglobulin</subject><subject>Immunoglobulin Idiotypes - biosynthesis</subject><subject>Immunoglobulin Idiotypes - immunology</subject><subject>Immunoglobulin M - biosynthesis</subject><subject>Immunoglobulin M - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Multiple Myeloma - immunology</subject><subject>Multiple Myeloma - pathology</subject><subject>Multiple Myeloma - therapy</subject><subject>myeloma</subject><subject>Neoplasm Transplantation</subject><subject>Receptors, Antigen, B-Cell - deficiency</subject><subject>Receptors, Antigen, B-Cell - immunology</subject><subject>vaccination</subject><issn>0818-9641</issn><issn>1440-1711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkc-KFDEQxoMo7rh69SgNgrceqzrp7uSog64LKx70HvKvnQzdyZh0s_TNR_AZfRKzOyOClz0VVfy-j6r6CHmJsEWg_G0-bL3R2x4BsKWPyAYZgxp7xMdkAxx5LTqGF-RZzgcA6BtOn5IL5Cjavuk2JF2leDvvKx_2XvvZx1DFoZpWN8ZJVcaNY670Wqkw-98_f3nr47we3X2vo_UuF2U178tEZxeMu1e7SScVXBHouARb-WlaQvw-Rr2MPjwnTwY1ZvfiXC_J148fvu0-1Tdfrq53725qwwBo3aDtjLADbV1rhWlbTjs3AKpGaME7q4TivOsMM6iVcaaxnHINgoNoqKKX5M3J9Zjij8XlWU4-391TFotLlj2w8qoWHgQb6ARrGBbw9X_gIS4plBMk9mUTRnvKCrU9USbFnJMb5DH5SaVVIsi7yGQ-yBKZPEdWBK_OtouenP2HnzMqQH8Cbv3o1gfs5PXn3fu_1n8A4tqmjw</recordid><startdate>200803</startdate><enddate>200803</enddate><creator>Moshitzky, Shiri</creator><creator>Kukulansky, Tova</creator><creator>Haimovich, Joseph</creator><creator>Hollander, Nurit</creator><general>Nature Publishing Group</general><general>Blackwell Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200803</creationdate><title>Growth inhibition of myeloma cells by anti‐idiotype antibodies in the absence of membrane‐bound immunoglobulin</title><author>Moshitzky, Shiri ; 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Plasma cells produce little or no membrane immunoglobulin but secrete immunoglobulin molecules in large amounts. Immunoglobulin idiotypes of malignant B cells are tumor‐specific antigens that may be targeted for immunotherapy. Thus, idiotype vaccination is being evaluated in clinical trials to control residual disease in multiple myeloma and non‐Hodgkin's lymphoma. It is traditionally considered that anti‐idiotype antibodies are not effective against plasma cell tumors, because the large amounts of immunoglobulin molecules secreted by the tumors block anti‐idiotype antibodies, and because the absence of membrane immunoglobulin on the surface of these tumor cells renders them resistant to the effect of anti‐idiotype antibodies. While the obstacle of abundant circulating idiotype may be obviated by reducing tumor burden to minimal residual disease, the absence of membrane immunoglobulin has been considered as a limiting factor that prevents tumor eradication by anti‐idiotype antibodies. We demonstrate here that murine plasmacytoma cells can produce small amounts of membrane immunoglobulin M (IgM) heavy chains. However, the latter are precursor molecules that do not reach the cell surface. Although membrane‐bound IgM is absent, the cells stain positively for surface IgM, reflecting molecules of the secreted form in the process of secretion. In spite of the relatively low levels of secreted immunoglobulin on the cell surface, anti‐idiotype antibodies are effective in retardation of tumor growth in vivo. Thus, while there is no doubt that idiotype‐specific cell‐mediated responses are very important, myeloma patients in complete remission may additionally benefit from idiotype‐specific humoral responses.</abstract><cop>United States</cop><pub>Nature Publishing Group</pub><pmid>18195726</pmid><doi>10.1038/sj.icb.7100153</doi><tpages>7</tpages></addata></record> |
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subjects | Animals Antibodies, Anti-Idiotypic - immunology Antibodies, Anti-Idiotypic - therapeutic use Antibody-Dependent Cell Cytotoxicity B cells Cancer Vaccines Cell Line, Tumor Cell Proliferation - drug effects idiotypes Immunization, Passive immunoglobulin Immunoglobulin Idiotypes - biosynthesis Immunoglobulin Idiotypes - immunology Immunoglobulin M - biosynthesis Immunoglobulin M - immunology Mice Mice, Inbred BALB C Mice, Inbred C3H Multiple Myeloma - immunology Multiple Myeloma - pathology Multiple Myeloma - therapy myeloma Neoplasm Transplantation Receptors, Antigen, B-Cell - deficiency Receptors, Antigen, B-Cell - immunology vaccination |
title | Growth inhibition of myeloma cells by anti‐idiotype antibodies in the absence of membrane‐bound immunoglobulin |
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