2013
DOI: 10.1371/journal.pone.0054923
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A Novel Angiopoietin-2 Selective Fully Human Antibody with Potent Anti-Tumoral and Anti-Angiogenic Efficacy and Superior Side Effect Profile Compared to Pan-Angiopoietin-1/-2 Inhibitors

Abstract: There is increasing experimental evidence for an important role of Angiopoietin-2 (Ang-2) in tumor angiogenesis and progression. In addition, Ang-2 is up-regulated in many cancer types and correlated with poor prognosis. To investigate the functional role of Ang-2 inhibition in tumor development and progression, we generated novel fully human antibodies that neutralize specifically the binding of Ang-2 to its receptor Tie2. The selected antibodies LC06 and LC08 recognize both rodent and human Ang-2 with high a… Show more

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Cited by 63 publications
(61 citation statements)
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“…Subsequently, the ability of the identified antibodies to interfere with ANG2-and ANG1-mediated TIE2 phosphorylation was examined. LC06 has been described previously (44). LC10 showed a dose-dependent interference with ANG2-stimulated TIE2 phosphorylation, with an EC50 value of 3 nM.…”
Section: Methodsmentioning
confidence: 92%
“…Subsequently, the ability of the identified antibodies to interfere with ANG2-and ANG1-mediated TIE2 phosphorylation was examined. LC06 has been described previously (44). LC10 showed a dose-dependent interference with ANG2-stimulated TIE2 phosphorylation, with an EC50 value of 3 nM.…”
Section: Methodsmentioning
confidence: 92%
“…Construction, expression and purification of Bs4Ab-VA, anti-VEGF and anti-Ang2 antibodies and isotype control antibody VH and VL sequences of anti-Ang2 LCO6 27 and anti-VEGF 28 were retrieved from USA patent application 2010/0111967. Amino acid sequences for the light and heavy chains of the Bs4Ab-VA used herein are shown in Fig.…”
Section: Methodsmentioning
confidence: 99%
“…We sought to determine whether the Bs4Ab design can be used to concurrently block VEGF and Ang2. The resulting molecule, Bs4Ab-VA, was prepared using an anti-Ang2 binding site from the antibody LCO6, 27 and an anti-VEGF binding site from bevacizumab. 28 In particular, the scFv domain of Bs4Ab-VA is from LCO6 and the Fab domain is from bevacizumab (Fig.…”
Section: Examples Of Antibodies Derived From the Bs4ab Technologymentioning
confidence: 99%
“…Here, we transfected HEK cells with plasmids in 1:1:1:1 ratios to co-express the 4 quadroma or KiH chains and analyzed the products by mass spectrometry for a comparative assessment. The underlying chains originate from anti-Ang-2 antibody LC06 (heavy chain denoted A and light chain a), 27 and bevacizumab 28 (Avastin Ò , heavy chain denoted B and light chain b), which are both isotype IgG1 with kappa C L . LC06 and bevacizumab are both HC allotype G1m1,17, and VH germlines: IGHV1-2-02 (99%) and IGHV3-23-04 (77%), and VL germlines: IGLV3-21-02 (97%) and IGKV1-16-01 or IGKV1-39-01 (88%), respectively.…”
Section: Introductionmentioning
confidence: 99%