title: Identification of Anti-EGFR and Anti-ErbB3 Dual Variable Domains Immunoglobulin (DVD-Ig) Proteins with Unique Activities.
abstract: 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.
authors.affiliation: AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, 01605, United States of America.
authors.forename: Jinming
authors.initials: J
authors.lastname: Gu
authors.affiliation: AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, 01605, United States of America.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Yang
authors.affiliation: AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, 01605, United States of America.
authors.forename: Qing
authors.initials: Q
authors.lastname: Chang
authors.affiliation: Cancer Research, R&D, AbbVie Inc., North Chicago, Illinois, 60064, United States of America.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, 01605, United States of America.
authors.forename: Tariq
authors.initials: T
authors.lastname: Ghayur
authors.affiliation: AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, 01605, United States of America.
authors.forename: Jijie
authors.initials: J
authors.lastname: Gu
mesh_terms: D018033:Antibodies, Bispecific / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000276:immunology*; D008024:Ligands; D020890:Neuregulin-1 / Q000378:metabolism; D011485:Protein Binding; D020893:Receptor, ErbB-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018033:Antibodies, Bispecific; D000970:Antineoplastic Agents; D007135:Immunoglobulin Variable Region; D008024:Ligands; D020890:Neuregulin-1; D011994:Recombinant Proteins; D066246:ErbB Receptors; D020893:Receptor, ErbB-3