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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1990-3-21
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pubmed:abstractText |
R24 is an IgG3 mouse monoclonal antibody which recognizes the ganglioside GD3. Two variants of R24, in which one (V2-R24) or both (V1-R24) light chains were substituted by MOPC-21 light chains, were isolated and characterized. R24 had a 40-fold higher avidity for GD3 than either variant, suggesting that high avidity binding required the presence of two R24 light chains and, thus, divalency. R24 and both variants mediated antibody-dependent cellular cytotoxicity but antibody-dependent cellular cytotoxicity mediated by variants was weak compared to R24. The presence of at least one R24 light chain was required for complement-dependent cytotoxicity; complement-dependent cytotoxicity was mediated by R24 and weakly by V2-R24 but not by V1-R24. R24, but not V1-R24 or V2-R24, inhibited attachment of melanoma cells to plastic and activated T-lymphocytes, suggesting a threshold of avidity required for these biological effects. In a human melanoma xenograft model in nu/nu mice, radiolabeled R24, variants, and isotype-matched control monoclonal antibodies all appeared to localize in tumors (based on tumor:normal tissue ratios), but specific tumor targeting by R24 was generally 3- to 6-fold higher. R24 prevented melanoma outgrowth in nu/nu mice, while V2-R24 induced partial tumor protection. V1-R24 and the negative control monoclonal antibody did not inhibit tumor outgrowth. Antitumor activity of R24 corresponded to avidity and ability to mediate complement-dependent cytotoxicity in vitro.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Gangliosides,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/ganglioside, GD3
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1503-9
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2105840-Animals,
pubmed-meshheading:2105840-Antibodies, Monoclonal,
pubmed-meshheading:2105840-Antibody Affinity,
pubmed-meshheading:2105840-Antibody-Dependent Cell Cytotoxicity,
pubmed-meshheading:2105840-Gangliosides,
pubmed-meshheading:2105840-Humans,
pubmed-meshheading:2105840-Immunoglobulin G,
pubmed-meshheading:2105840-Immunoglobulin Light Chains,
pubmed-meshheading:2105840-Lymphocyte Activation,
pubmed-meshheading:2105840-Melanoma,
pubmed-meshheading:2105840-Mice,
pubmed-meshheading:2105840-Molecular Weight,
pubmed-meshheading:2105840-Neoplasm Transplantation,
pubmed-meshheading:2105840-Tumor Cells, Cultured
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pubmed:year |
1990
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pubmed:articleTitle |
Light chain variants of an IgG3 anti-GD3 monoclonal antibody and the relationship among avidity, effector functions, tumor targeting, and antitumor activity.
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pubmed:affiliation |
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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