|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2000-11-3
|
|
pubmed:abstractText |
Anti-HER2/neu therapy of human HER2/neu-expressing malignancies such as breast cancer has shown only partial success in clinical trials. To expand the clinical potential of this approach, we have genetically engineered an anti-HER2/neu IgG3 fusion protein containing GM-CSF. Anti-HER2/neu IgG3-(GM-CSF) expressed in myeloma cells was correctly assembled and secreted. It was able to target HER2/neu-expressing cells and to support growth of a GM-CSF-dependent murine myeloid cell line, FDC-P1. The Ab fusion protein activated J774.2 macrophage cells so that they exhibit an enhanced cytotoxic activity and was comparable to the parental Ab in its ability to effect Ab-dependent cellular cytotoxicity-mediated tumor cell lysis. Pharmacokinetic studies showed that anti-HER2/neu IgG3-(GM-CSF) is stable in the blood. Interestingly, the half-life of anti-HER2/neu IgG3-(GM-CSF) depended on the injected dose with longer in vivo persistence observed at higher doses. Biodistribution studies showed that anti-HER2/neu IgG3-(GM-CSF) is mainly localized in the spleen. In addition, anti-HER2/neu IgG3-(GM-CSF) was able to target the HER2/neu-expressing murine tumor CT26-HER2/neu and enhance the immune response against the targeted Ag HER2/neu. Anti-HER2/neu IgG3-(GM-CSF) is able to enhance both Th1- and Th2-mediated immune responses and treatment with this Ab fusion protein resulted in significant retardation in the growth of s.c. CT26-HER2/neu tumors. Our results suggest that anti-HER2/neu IgG3-(GM-CSF) fusion protein is useful in the treatment of HER2/neu-expressing tumors.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Anti-Idiotypic,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
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/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/anti-IgG
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
165
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
5112-21
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:11046042-Adenocarcinoma,
pubmed-meshheading:11046042-Animals,
pubmed-meshheading:11046042-Antibodies, Anti-Idiotypic,
pubmed-meshheading:11046042-Antibodies, Neoplasm,
pubmed-meshheading:11046042-Antineoplastic Agents,
pubmed-meshheading:11046042-Cell Division,
pubmed-meshheading:11046042-Cell Line,
pubmed-meshheading:11046042-Cell Membrane,
pubmed-meshheading:11046042-Colonic Neoplasms,
pubmed-meshheading:11046042-Cytokines,
pubmed-meshheading:11046042-Cytotoxicity, Immunologic,
pubmed-meshheading:11046042-Epitopes,
pubmed-meshheading:11046042-Female,
pubmed-meshheading:11046042-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:11046042-Half-Life,
pubmed-meshheading:11046042-Humans,
pubmed-meshheading:11046042-Immunoglobulin G,
pubmed-meshheading:11046042-Immunoglobulin Isotypes,
pubmed-meshheading:11046042-Injections, Intravenous,
pubmed-meshheading:11046042-Injections, Subcutaneous,
pubmed-meshheading:11046042-Macrophages,
pubmed-meshheading:11046042-Mice,
pubmed-meshheading:11046042-Mice, Inbred BALB C,
pubmed-meshheading:11046042-Protein Binding,
pubmed-meshheading:11046042-Receptor, erbB-2,
pubmed-meshheading:11046042-Recombinant Fusion Proteins,
pubmed-meshheading:11046042-Tumor Cells, Cultured
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
Recombinant anti-human HER2/neu IgG3-(GM-CSF) fusion protein retains antigen specificity and cytokine function and demonstrates antitumor activity.
|
|
pubmed:affiliation |
Departments of Microbiology and Molecular Genetics, and The Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|
