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Intracellular uptake and catabolism of anti-IgM antibodies and bi-specific antibody-targeted hapten by B-lymphoma cells.

Identifieur interne : 004665 ( Main/Exploration ); précédent : 004664; suivant : 004666

Intracellular uptake and catabolism of anti-IgM antibodies and bi-specific antibody-targeted hapten by B-lymphoma cells.

Auteurs : RBID : pubmed:7591213

English descriptors

Abstract

The efficiency of radioimmunotherapy with iodine-labelled antibodies is often limited by intracellular internalisation and catabolism after initial binding to the cellular targets. We have developed a technique called affinity enhancement system (AES) which uses bi-specific antibodies to target radiolabelled bivalent haptens to cells. This targeting method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigated the potential of this technique to target iodine radioisotopes by comparing it to targeting with covalently iodine-labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B-lymphoma cell line. A 5-fold increase in the intracellular retention time of activity as compared to 125I-labelled F(ab')2 or IgG was observed. The radiolabelled hapten did not undergo any catabolism after internalisation. Resistance to cellular proteases and failure of recognition of the hapten by amino acid transporter systems may be potential explanations for these observations. This should make non-covalent targeting, particularly the AES, a method of choice to target modulating antigens for the therapy of malignant hemopathies.

PubMed: 7591213

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Le document en format XML

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<title xml:lang="en">Intracellular uptake and catabolism of anti-IgM antibodies and bi-specific antibody-targeted hapten by B-lymphoma cells.</title>
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<name sortKey="Manetti, C" uniqKey="Manetti C">C Manetti</name>
<affiliation wicri:level="1">
<nlm:affiliation>IMMUNOTECH S.A., Marseille, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>IMMUNOTECH S.A., Marseille</wicri:regionArea>
<placeName>
<region type="région">Provence-Alpes-Côte d'Azur</region>
<settlement type="city">Marseille</settlement>
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<author>
<name sortKey="Le Doussal, J M" uniqKey="Le Doussal J">J M Le Doussal</name>
</author>
<author>
<name sortKey="Rouvier, E" uniqKey="Rouvier E">E Rouvier</name>
</author>
<author>
<name sortKey="Gruaz Guyon, A" uniqKey="Gruaz Guyon A">A Gruaz-Guyon</name>
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<author>
<name sortKey="Barbet, J" uniqKey="Barbet J">J Barbet</name>
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<term>Antibodies, Anti-Idiotypic (metabolism)</term>
<term>Antibodies, Bispecific (metabolism)</term>
<term>Cells, Cultured</term>
<term>Endocytosis</term>
<term>Haptens (metabolism)</term>
<term>Humans</term>
<term>Hydrogen-Ion Concentration</term>
<term>Immunoglobulin M (immunology)</term>
<term>Indium Radioisotopes (diagnostic use)</term>
<term>Iodine Radioisotopes (diagnostic use)</term>
<term>Lymphoma, B-Cell (metabolism)</term>
<term>Receptors, Antigen, B-Cell (immunology)</term>
<term>Receptors, Antigen, B-Cell (metabolism)</term>
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<keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en">
<term>Indium Radioisotopes</term>
<term>Iodine Radioisotopes</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en">
<term>Immunoglobulin M</term>
<term>Receptors, Antigen, B-Cell</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Antibodies, Anti-Idiotypic</term>
<term>Antibodies, Bispecific</term>
<term>Haptens</term>
<term>Receptors, Antigen, B-Cell</term>
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<keywords scheme="MESH" qualifier="metabolism" xml:lang="en">
<term>Lymphoma, B-Cell</term>
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<keywords scheme="MESH" xml:lang="en">
<term>Cells, Cultured</term>
<term>Endocytosis</term>
<term>Humans</term>
<term>Hydrogen-Ion Concentration</term>
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<div type="abstract" xml:lang="en">The efficiency of radioimmunotherapy with iodine-labelled antibodies is often limited by intracellular internalisation and catabolism after initial binding to the cellular targets. We have developed a technique called affinity enhancement system (AES) which uses bi-specific antibodies to target radiolabelled bivalent haptens to cells. This targeting method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigated the potential of this technique to target iodine radioisotopes by comparing it to targeting with covalently iodine-labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B-lymphoma cell line. A 5-fold increase in the intracellular retention time of activity as compared to 125I-labelled F(ab')2 or IgG was observed. The radiolabelled hapten did not undergo any catabolism after internalisation. Resistance to cellular proteases and failure of recognition of the hapten by amino acid transporter systems may be potential explanations for these observations. This should make non-covalent targeting, particularly the AES, a method of choice to target modulating antigens for the therapy of malignant hemopathies.</div>
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<Year>2007</Year>
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<ISSN IssnType="Print">0020-7136</ISSN>
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<Volume>63</Volume>
<Issue>2</Issue>
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<Year>1995</Year>
<Month>Oct</Month>
<Day>9</Day>
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<Title>International journal of cancer. Journal international du cancer</Title>
<ISOAbbreviation>Int. J. Cancer</ISOAbbreviation>
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<ArticleTitle>Intracellular uptake and catabolism of anti-IgM antibodies and bi-specific antibody-targeted hapten by B-lymphoma cells.</ArticleTitle>
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<AbstractText>The efficiency of radioimmunotherapy with iodine-labelled antibodies is often limited by intracellular internalisation and catabolism after initial binding to the cellular targets. We have developed a technique called affinity enhancement system (AES) which uses bi-specific antibodies to target radiolabelled bivalent haptens to cells. This targeting method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigated the potential of this technique to target iodine radioisotopes by comparing it to targeting with covalently iodine-labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B-lymphoma cell line. A 5-fold increase in the intracellular retention time of activity as compared to 125I-labelled F(ab')2 or IgG was observed. The radiolabelled hapten did not undergo any catabolism after internalisation. Resistance to cellular proteases and failure of recognition of the hapten by amino acid transporter systems may be potential explanations for these observations. This should make non-covalent targeting, particularly the AES, a method of choice to target modulating antigens for the therapy of malignant hemopathies.</AbstractText>
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