Document Detail


Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2.
MedLine Citation:
PMID:  24003140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Due to intrinsic aggressiveness and lack of effective therapies, prognosis of pancreatic cancer remains dismal. Because the only molecular targeted drug approved for pancreatic ductal adenocarcinoma is a kinase inhibitor specific to the epidermal growth factor receptor (EGFR), and this receptor collaborates with another kinase, called HER2 (human EGF-receptor 2), we assumed that agents targeting EGFR and/or HER2 would effectively retard pancreatic ductal adenocarcinoma. Accordingly, two immunological strategies were tested in animal models: (i) two antibodies able to engage distinct epitopes of either EGFR or HER2 were separately combined, and (ii) pairs of one antibody to EGFR and another to HER2. Unlike the respective single monoclonal antibodies, which induced weak effects, both types of antibody combinations synergized in animals in terms of tumor inhibition. Immunological cooperation may not depend on receptor density, antigenic sites, or the presence of a mutant RAS protein. Nevertheless, both types of antibody combinations enhanced receptor degradation. Future efforts will examine the feasibility of each strategy and the potential of combining them to achieve sustained tumor inhibition.
Authors:
Ruth Maron; Bilha Schechter; Maicol Mancini; Georg Mahlknecht; Yosef Yarden; Michael Sela
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-09-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  110     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-09-18     Completed Date:  2013-11-26     Revised Date:  2014-03-23    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15389-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Antibodies, Monoclonal / immunology,  therapeutic use*
Carcinoma, Pancreatic Ductal / drug therapy*,  immunology
Drug Synergism
Female
Fluorescent Antibody Technique
Mice
Mice, Nude
Receptor, Epidermal Growth Factor / immunology*
Receptor, erbB-2 / immunology*
Signal Transduction / immunology*
Grant Support
ID/Acronym/Agency:
CA072981/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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