PMID: 21827946

 

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

Abstract :
  1. The anti- VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer
  2. 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
  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
  4. Mutagenesis reveals that residues essential for VEGF , 1121B, and 6.64 binding are nonoverlapping among the three contact patches