Title : The structural basis for the function of two anti-
VEGF receptor 2 antibodies
Abstract :
- 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