Identification of anti-ErbB2 dual variable domain immunoglobulin (DVD-Ig™) proteins with unique activities.
Inhibiting ErbB2 signaling with monoclonal antibodies (mAbs) or small molecules is an established therapeutic strategy in oncology. We have developed anti-ErbB2 Dual Variable Domain Immunoglobulin (DVD-Ig) proteins that capture the function of a combination of two anti-ErbB2 antibodies. In addition, some of the anti-ErbB2 DVD-Ig proteins gain the new functions of enhancing ErbB2 signaling and cell proliferation in N87 cells. We further found that two DVD-Ig proteins, DVD687 and DVD688, have two distinct mechanisms of actions in Calu-3 and N87 cells. DVD687 enhances cell cycle progression while DVD688 induces apoptosis in N87 cells. Using a half DVD687, we found that avidity may play a key role in the agonist activity of DVD687 in N87 cells.
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Jinming
J
Gu
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Jinsong
J
Yang
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Qing
Q
Chang
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Xiaoqing
X
Lu
Cancer Research, R&D, AbbVie Inc., North Chicago, Illinois, United States of America.
Jieyi
J
Wang
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Mingjiu
M
Chen
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Tariq
T
Ghayur
AbbVie Bioresearch Center, R&D, Worcester, Massachusetts, United States of America.
Jijie
J
Gu
D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001973:Bromodeoxyuridine; D002460:Cell Line; D019281:Dimerization; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D047468:Immunoprecipitation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D001973:Bromodeoxyuridine; D007136:Immunoglobulins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human