Identification of a human antibody 3.19.3 that inhibits ANG-2 function leading to significant anti-tumour activity, both alone and in combination with VEGF inhibitors, in a panel of tumour xenograft models


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David Blakey1, Steve Emery1, Joe Zhou2, Jane Kendrew1, Corinne Reimer3, Alex Cao3, Andy Ryan1, Juliane Jrgensmeier1, Jeff Brown3

1AstraZeneca, Alderley Park, Macclesfield, UK, 2Abgenix Inc., Fremont, California, USA, 3AstraZeneca, GateHouse Park, Waltham, USA

Abstract

ANG-2 expression and association with sites of vascular remodelling in tumours, and limited expression in normal tissues, make it a very attractive candidate for anti-angiogenic cancer therapy. Antibody 3.19.3 was generated using Abgenixs XenomouseTM technology and potently blocks binding of ANG-2 to the Tie2 receptor (IC50 = 478 pM) and inhibits Tie2 receptor phosphorylation in HEK129F/Tie2 expressing cells (IC50 = 580 pM).