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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Veröffentlicht in:Immunology and cell biology 2008-03, Vol.86 (3), p.261-267
Hauptverfasser: Moshitzky, Shiri, Kukulansky, Tova, Haimovich, Joseph, Hollander, Nurit
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container_title Immunology and cell biology
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creator Moshitzky, Shiri
Kukulansky, Tova
Haimovich, Joseph
Hollander, Nurit
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.
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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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