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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0009498,
umls-concept:C0022646,
umls-concept:C0024348,
umls-concept:C0041361,
umls-concept:C0108793,
umls-concept:C0206491,
umls-concept:C0333562,
umls-concept:C0431085,
umls-concept:C0439851,
umls-concept:C0597032,
umls-concept:C0910225,
umls-concept:C1552596,
umls-concept:C1704735,
umls-concept:C1947931,
umls-concept:C2349975
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pubmed:issue |
7
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pubmed:dateCreated |
1998-4-21
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pubmed:abstractText |
Tumor cells may inhibit the induction of a complement-mediated inflammatory response through overexpression of membrane-bound regulators of complement activation. Therefore, it is of interest to determine the most efficient approach to block these membrane-bound complement regulators on tumor cells. In the present study, we first generated a bispecific mAb directed against both CD55, using the functional blocking mAb MBC1, and the highly expressed HLA class I molecule as a model for a tumor-associated Ag, using the mAb W6/32. Tumor cells opsonized with bispecific mAb W6/32*MBC1, then exposed to complement and subsequently stained for C3 deposition, were assessed by flow cytometric analysis. We found that opsonization with W6/32*MBC1 resulted in a 92% enhancement of C3 deposition on renal tumor cells as compared with opsonization with W6/32 alone and a 17% enhancement of the C3 deposition as compared with incubation with a mixture of both parental mAb. Based on these results, we developed a bispecific mAb recognizing both CD55 and the relatively low expressed renal tumor-associated Ag G250. Increasing concentrations of the bispecific mAb G250*MBC1 resulted in a 25 to 400% increase in C3 deposition on renal tumor cells as compared with C3 deposition in the presence of the parental mAb G250 alone. G250*MBC1 enhanced C3 deposition by 21% in comparison with a mixture of both parentals. Furthermore, opsonization of tumor cells with G250*MBC1 rendered these cells more sensitive to complement-mediated lysis. In conclusion, the bispecific mAb G250*MBC1 induces deposition of C3 and tumor cell lysis more efficiently than G250 alone.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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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/Antigens, CD55,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Complement C3,
http://linkedlifedata.com/resource/pubmed/chemical/Complement Inactivator Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Complement System Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/G250 monoclonal antibody
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
160
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3437-43
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pubmed:dateRevised |
2011-7-29
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pubmed:meshHeading |
pubmed-meshheading:9531304-Antibodies, Bispecific,
pubmed-meshheading:9531304-Antibodies, Monoclonal,
pubmed-meshheading:9531304-Antigens, CD55,
pubmed-meshheading:9531304-Antigens, Neoplasm,
pubmed-meshheading:9531304-Cell Membrane,
pubmed-meshheading:9531304-Clone Cells,
pubmed-meshheading:9531304-Complement Activation,
pubmed-meshheading:9531304-Complement C3,
pubmed-meshheading:9531304-Complement Inactivator Proteins,
pubmed-meshheading:9531304-Complement System Proteins,
pubmed-meshheading:9531304-Cytotoxicity, Immunologic,
pubmed-meshheading:9531304-Humans,
pubmed-meshheading:9531304-Kidney Neoplasms,
pubmed-meshheading:9531304-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
A bispecific monoclonal antibody directed against both the membrane-bound complement regulator CD55 and the renal tumor-associated antigen G250 enhances C3 deposition and tumor cell lysis by complement.
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pubmed:affiliation |
Department of Pathology, Leiden University Hospital, The Netherlands. vblok@path_1.medfac.leidenuniv.nl
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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