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rdf:type |
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lifeskim:mentions |
umls-concept:C0003320,
umls-concept:C0025936,
umls-concept:C0086418,
umls-concept:C0599894,
umls-concept:C0871261,
umls-concept:C1414550,
umls-concept:C1414551,
umls-concept:C1414552,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1762617,
umls-concept:C2911692
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pubmed:issue |
12
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pubmed:dateCreated |
2000-12-21
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pubmed:abstractText |
Previous studies have documented that targeting foreign Ags to IgG FcgammaR leads to enhanced Ag-specific responses in vitro and in vivo. However, the ability to overcome immunologic nonresponsiveness by targeting poorly immunogenic Ags to FcgammaR has not been investigated. To address this question in a simple model, we immunized transgenic mice expressing human CD64 (FcgammaRI) and their nontransgenic littermates with Fab' derived from the murine anti-human CD64 mAb m22. The m22 Fab' served as both the targeting molecule and the Ag. We found that only CD64-expressing mice developed anti-Id titers to m22. Furthermore, chemically linked multimers of m22 Fab', which mediated efficient internalization of the human CD64, were significantly more potent than monomeric m22 F(ab')(2) at inducing anti-Id responses. In all cases, the humoral responses were specific for m22 Id and did not react with other murine IgG1 Fab' fragments. Chemical addition of a second murine Fab' (520C9 anti-human HER2/neu) to m22 Fab' multimers demonstrated that IgG1 and IgG2a anti-Id titers could be generated to 520C9 only in the CD64-expressing mice. These results show that targeting to CD64 can overcome immunological nonresponsiveness to a weak immunogen. Therefore, targeting to CD64 may be an effective method to enhance the activity of nonimmunogenic tumor vaccines.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Anti-Idiotypic,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Isotypes,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, erbB-2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, IgG
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
165
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6738-42
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11120792-Animals,
pubmed-meshheading:11120792-Antibodies, Anti-Idiotypic,
pubmed-meshheading:11120792-Antibodies, Monoclonal,
pubmed-meshheading:11120792-Antibody Specificity,
pubmed-meshheading:11120792-Antigens,
pubmed-meshheading:11120792-Binding Sites, Antibody,
pubmed-meshheading:11120792-Dose-Response Relationship, Immunologic,
pubmed-meshheading:11120792-Female,
pubmed-meshheading:11120792-Humans,
pubmed-meshheading:11120792-Immunoglobulin Fab Fragments,
pubmed-meshheading:11120792-Immunoglobulin G,
pubmed-meshheading:11120792-Immunoglobulin Isotypes,
pubmed-meshheading:11120792-Mice,
pubmed-meshheading:11120792-Mice, Inbred Strains,
pubmed-meshheading:11120792-Mice, Transgenic,
pubmed-meshheading:11120792-Models, Immunological,
pubmed-meshheading:11120792-Receptor, erbB-2,
pubmed-meshheading:11120792-Receptors, IgG,
pubmed-meshheading:11120792-Time Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Targeting weak antigens to CD64 elicits potent humoral responses in human CD64 transgenic mice.
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pubmed:affiliation |
Medarex, Inc., Annandale, NJ 08801, USA. tkeler@injersey.com
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pubmed:publicationType |
Journal Article
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