Inhibition of pancreatic carcinoma by homo-and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2

Ruth Maron, Bilha Schechter, Maicol Mancini, Georg Mahlknecht, Yosef Yarden, Michael Sela

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)15389-15394
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number38
DOIs
StatePublished - 17 Oct 2013

All Science Journal Classification (ASJC) codes

  • General

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