Open AccessIdentification of Anti-EGFR and Anti-ErbB3 Dual Variable Domains Immunoglobulin (DVD-Ig) Proteins with Unique Activities
Author(s) -
Jinming Gu,
Jingye Yang,
Qing Chang,
Zhihong Liu,
Tariq Ghayur,
Jijie Gu
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0124135
Subject(s) - erbb3 , neuregulin , internalization , epidermal growth factor receptor , receptor , microbiology and biotechnology , tyrosine kinase , biology , neuregulin 1 , downregulation and upregulation , antibody , a431 cells , receptor tyrosine kinase , cancer research , signal transduction , chemistry , cell , cell cycle , immunology , biochemistry , oncogene , gene
Epidermal growth factor receptor (EGFR) and receptor tyrosine-protein kinase 3 (ErbB3) are two well-established targets in cancer therapy. There is significant crosstalk among these two receptors and others. To block signaling from both EGFR and ErbB3, we generated anti-EGFR and anti-ErbB3 DVD-Ig proteins. Two DVD-Ig proteins maintained the functions of the combination of the two parental antibodies. The DVD-Ig proteins inhibit cell signaling and proliferation in A431 and FaDu cells while half DVD-Ig proteins lost proliferation inhibition function. Interestingly, in the presence of β-Heregulin (HRG), the DVD-Ig proteins show synergies with respect to inhibiting cell proliferation. The DVD-Ig proteins downregulate EGFR protein expression in the presence of HRG, which may be due to receptor internalization. Furthermore, the DVD-Ig proteins remarkably disrupt β-Heregulin binding to FaDu cells.