The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

Journal Article · Sat Dec 31 04:00:00 EST 2011 · Structure

DOI:https://doi.org/10.1016/j.str.2011.01.019· OSTI ID:1042091

Franklin, M; Navarro, E; Wang, Y; Patel, S; Singh, P; Zhang, Y; Persaud, K; Bari, A; Griffith, H

The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

• Research Organization: BROOKHAVEN NATIONAL LABORATORY (BNL)
• Sponsoring Organization: USDOE SC OFFICE OF SCIENCE (SC)
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 1042091
• Report Number(s): BNL--97769-2012-JA
• Journal Information: Structure, Journal Name: Structure Journal Issue: 8 Vol. 19; ISSN 0969-2126
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
DIMERIZATION
MAMMARY GLANDS
MUTAGENESIS
NEOPLASMS
RESIDUES