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Novel anti‐ErbB3 monoclonal antibodies show therapeutic efficacy in xenografted and spontaneous mouse tumors
Author(s) -
Aurisicchio Luigi,
Marra Emanuele,
Luberto Laura,
Carlomosti Fabrizio,
De Vitis Claudia,
Noto Alessia,
Gunes Zeynep,
Roscilli Giuseppe,
Mesiti Giuseppe,
Mancini Rita,
Alimandi Maurizio,
Ciliberto Gennaro
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24037
Subject(s) - erbb3 , monoclonal antibody , erbb , cancer research , receptor tyrosine kinase , signal transduction , biology , tyrosine kinase inhibitor , tyrosine kinase , receptor , antibody , cancer , microbiology and biotechnology , immunology , biochemistry , genetics
The role of the ErbB3 receptor in signal transduction is to augment the signaling repertoire of active heterodimeric ErbB receptor complexes through activating the PI3K/AKT pathway, which in turn promotes survival and proliferation. ErbB3 has recently been proposed to be involved in acquired resistance to tyrosine kinase inhibitors (TKIs), and is therefore a promising new drug cancer target. Since ErbB3 is a kinase defective receptor, it cannot be targeted by small molecule inhibitors, whereas monoclonal antibodies may offer a viable strategy for pharmacological intervention. In this study, we have utilized DNA electroporation (DNA‐EP) to generate a set of novel hybridomas directed against human ErbB3, which have been characterized for their biochemical and functional properties and selected for their ability to negatively regulate the ErbB3‐mediated signaling pathway. In vitro, the anti‐ErbB3 antibodies modulate the growth rate of cancer cells of different origins. In vivo they show antitumoral properties in a xenograft model of human pancreatic tumor and in the ErbB2‐driven carcinogenesis genetically engineered mouse model (GEMM) for mammary tumor, the BALB/ neuT . Our data confirm that downregulating the ErbB3‐mediated signals with the use of anti‐ErbB3 monoclonal antibodies is both feasible and relevant for therapeutic purposes and provides new opportunities for novel anti‐ErbB3 combinatory strategies for cancer treatment. J. Cell. Physiol. 227: 3381–3388, 2012. © 2011 Wiley Periodicals, Inc.