Source:http://linkedlifedata.com/resource/pubmed/id/10188732
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1999-4-13
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pubmed:abstractText |
In an attempt to improve tumor targeting and tumor retention time of monoclonal antibodies (MAbs), we prepared biparatopic antibodies (BpAbs) having the capability of binding 2 different non-overlapping epitopes on the same target antigen molecule, namely, the carcinoembryonic antigen (CEA). Six BpAbs were constructed by coupling 2 different Fab' fragments from 4 different specific anti-CEA MAbs recognizing 4 CEA epitopes (Gold 1-4). Demonstration of the double paratopic binding of these antibodies for CEA was confirmed in vitro by inhibition radioimmunoassay and cross-inhibition analysis by surface plasmon resonance (SPR; BIACORE) technology. Using the latter technique, the affinity constants for CEA immobilized onto the sensor chip were found to range from 0.37 to 1.54 x 10(9) M(-1) for the 4 parental F(ab')2 fragments and from 1.88 to 10.14 x 10(9) M(-1) for the BpAbs, demonstrating the advantage of biparatopic binding over conventional F(ab')2 binding. The Ka improvement was particularly high for BpAb F6/35A7 and BpAb F6/B17 with a 9.5- and 8.1-fold increase, respectively, as compared with the parental F(ab')2. In vivo, the 6 BpAbs were compared with their 2 respective parental F(ab')2 by injection of 131I-BpAb/125I-F(ab')2 parental fragments into nude mice xenografted with the human colon carcinoma T380. Dissection 72 hr post-injection demonstrated that BpAb B17/CE25 and BpAb F6/B17 gave higher tumor uptake than that of their parental F(ab')2. This finding is particularly interesting for BpAb F6/B17, which compared favorably with the F6 F(ab')2, one of the best parental F(ab')2 fragments used in our study.
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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, Bispecific,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinoembryonic Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0020-7136
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
81
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
285-91
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:10188732-Animals,
pubmed-meshheading:10188732-Antibodies, Bispecific,
pubmed-meshheading:10188732-Antibodies, Monoclonal,
pubmed-meshheading:10188732-Carcinoembryonic Antigen,
pubmed-meshheading:10188732-Epitopes,
pubmed-meshheading:10188732-Humans,
pubmed-meshheading:10188732-Immunoglobulin Fab Fragments,
pubmed-meshheading:10188732-Kinetics,
pubmed-meshheading:10188732-Mice,
pubmed-meshheading:10188732-Mice, Nude,
pubmed-meshheading:10188732-Transplantation, Heterologous,
pubmed-meshheading:10188732-Tumor Cells, Cultured
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pubmed:year |
1999
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pubmed:articleTitle |
Tumor targeting with newly designed biparatopic antibodies directed against two different epitopes of the carcinoembryonic antigen (CEA).
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pubmed:affiliation |
Cancer Research Center, Institute Val d'Aurelle-Paul Lamarque, Montpellier, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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