TY - JOUR
T1 - Inhibition of pancreatic carcinoma by homo-and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2
AU - Maron, Ruth
AU - Schechter, Bilha
AU - Mancini, Maicol
AU - Mahlknecht, Georg
AU - Yarden, Yosef
AU - Sela, Michael
N1 - US National Cancer Institute [CA072981]; European Research Council; Seventh Framework Program of the European Commission; German-Israeli Project Cooperation (DIP); Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; M.D. Moross Cancer Institute; Julius Baer Trust; Dukler Mudy Grant; Sergio Lombroso FoundationWe thank Dr. Rachel Heibloom for statistical analyses. This work was supported by grants from the US National Cancer Institute (CA072981), the European Research Council, the Seventh Framework Program of the European Commission, the German-Israeli Project Cooperation (DIP), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the M.D. Moross Cancer Institute, and the Julius Baer Trust; and a Dukler Mudy Grant. G.M. acknowledges the support of the Sergio Lombroso Foundation. M. S. is the incumbent of the W. Garfield Weston Chair. Y.Y. is a Research Professor of the Israel Cancer Research fund, and the incumbent of the Harold and Zelda Goldenberg Professorial Chair.
PY - 2013/10/17
Y1 - 2013/10/17
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84884319673&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.1313857110
DO - https://doi.org/10.1073/pnas.1313857110
M3 - مقالة
SN - 0027-8424
VL - 110
SP - 15389
EP - 15394
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 38
ER -