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PMID: 19218427 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies: relevance of receptor endocytosis.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 106 ·No. 9 ·2009-03-03 ·Pages 3294-9

Ben-Kasus T, Schechter B, Lavi S, Yarden Y, Sela M

Abstract

Monoclonal antibodies (mAbs) to ErbB-2/HER2 or to its sibling, the epidermal growth factor receptor (EGFR), prolong survival of cancer patients, especially when combined with cytotoxic therapies. However, low effectiveness of therapeutic mAbs and the evolution of patient resistance call for improvements. Here we test in animals pairs of anti-ErbB-2 mAbs and report that pairs comprising an antibody reactive with the dimerization site of ErbB-2 and an antibody recognizing another distinct epitope better inhibit ErbB-2-overexpressing tumors than other pairs or the respective individual mAbs. Because the superiority of antibody combinations extends to tumor cell cultures, we assume that nonimmunological mechanisms contribute to mAb synergy. One potential mechanism, namely the ability of mAb combinations to instigate ErbB-2 endocytosis, is demonstrated. Translation of these lessons to clinical applications may enhance patient response and delay acquisition of resistance.

MeSH Terms
Antibodies, Monoclonal/immunology Antibody Specificity Cell Line, Tumor Cell Proliferation Endocytosis/immunology Epitopes/immunology Humans Neoplasms/genetics,immunology,metabolism,pathology Receptor, ErbB-2/genetics,immunology,metabolism
Chemicals
Antibodies, Monoclonal Epitopes Receptor, ErbB-2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ben-Kasus Tsipi
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Schechter Bilha
Lavi Sara
Yarden Yosef
Sela Michael
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.0812059106
Published
2009-03-03
Epub
2009-00-13
Pages
3294-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2651295
Subset
IM
Grants
NCI NIH HHS · R01 CA072981 · United States
NCI NIH HHS · R37 CA072981 · United States
NCI NIH HHS · CA72981 · United States
External Links
PubMed source DOI: 10.1073/pnas.0812059106 PMC Full Text View journal details
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