Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7
|
| pubmed:dateCreated |
1994-4-28
|
| pubmed:abstractText |
The monoclonal antibodies (MAbs) 323/A3 and 17-1A both recognize a 40-kDa carcinoma-associated epithelial glycoprotein (EGP40). MAb 17-1A has been used in many therapeutic trials as an immunotherapeutic agent to combat advanced colorectal cancer, and about 5-10% overall responses have been observed. It has been shown that MAb 323/A3 has a higher affinity than 17-1A, which might be an advantageous feature for a therapeutic agent. In our immunohistological studies different reaction patterns of these two MAbs were observed, suggesting that MAb 323/A3 reacts more intensely with carcinoma cells than MAb 17-1A. This also suggests that MAb 323/A3 might be a more effective immunotherapeutic tool. Because chimerization may reduce the immunogenicity of the murine MAb 323/A3 and increase the interaction with human effector mechanisms, we developed a chimeric form of murine MAb 323/A3. MAb 323/A3 heavy and light chain variable genes were cloned and grafted onto human C gamma 1 and C kappa domains, respectively. A chimeric antibody-producing cell line was established by transfection of the chimeric constructs into a nonproducing myeloma cell. The chimeric and murine 323/A3 MAbs were evaluated for efficacy of inducing complement-mediated cytotoxicity (CMC) and mediating antibody-dependent cellular cytotoxicity against LS 180 cells derived from human colon carcinoma. Both forms were found to mediate similar levels of CMC in the presence of human complement; however, higher levels of lysis of target cells were observed with human peripheral blood lymphocytes when the chimeric 323/A3 was used. Chimeric 323/A3 mediated higher maximal cytotoxicity than chimeric 17-1A in both CMC and antibody-dependent cellular cytotoxicity assays and was equally active as chimeric 17-1A at 100- to 1000-fold lower concentrations. The superior reactivity of chimeric 323/A3 with EGP40 on carcinoma cells and its higher cytotoxicity-mediating capacity, compared to chimeric 17-1A, are important characteristics, which support further clinical studies with chimeric MAb 323/A3 in immunotherapy of carcinomas.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Probes,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Constant Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Heavy Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Light Chains,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Variable Region,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/carcinoma-associated antigen 17-1A,
http://linkedlifedata.com/resource/pubmed/chemical/tumor-associated antigen GA733
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0008-5472
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
54
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1753-9
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:8137290-Adenocarcinoma,
pubmed-meshheading:8137290-Animals,
pubmed-meshheading:8137290-Antibodies, Monoclonal,
pubmed-meshheading:8137290-Antigens, Neoplasm,
pubmed-meshheading:8137290-Cell Adhesion Molecules,
pubmed-meshheading:8137290-Cell Survival,
pubmed-meshheading:8137290-Colonic Neoplasms,
pubmed-meshheading:8137290-DNA Probes,
pubmed-meshheading:8137290-Genes, Immunoglobulin,
pubmed-meshheading:8137290-Humans,
pubmed-meshheading:8137290-Hybridomas,
pubmed-meshheading:8137290-Immunoglobulin Constant Regions,
pubmed-meshheading:8137290-Immunoglobulin Heavy Chains,
pubmed-meshheading:8137290-Immunoglobulin Light Chains,
pubmed-meshheading:8137290-Immunoglobulin Variable Region,
pubmed-meshheading:8137290-Mice,
pubmed-meshheading:8137290-Multiple Myeloma,
pubmed-meshheading:8137290-Recombinant Fusion Proteins,
pubmed-meshheading:8137290-Tumor Cells, Cultured
|
| pubmed:year |
1994
|
| pubmed:articleTitle |
New chimeric anti-pancarcinoma monoclonal antibody with superior cytotoxicity-mediating potency.
|
| pubmed:affiliation |
Department of Pathology, State University Leiden, The Netherlands.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|