VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade

摘要: VEGF is the best characterized mediator of tumor angiogenesis. Anti-VEGF agents have recently demonstrated impressive efficacy in human cancer trials, but optimal dosing such must still be determined empirically, because biomarkers to guide yet established. The widely accepted (but unverified) assumption that production quite low normal adults led notion increased systemic levels might quantitatively reflect mass and angiogenic activity. We describe an approach determine host VEGF, using a high-affinity long-lived antagonist now clinical Trap. Unlike antibody complexes are usually rapidly cleared, Trap forms inert with tissue- tumor-derived remain stably circulation, where they readily assayable, providing unprecedented capability accurately measure production. report surprisingly high non-tumor-bearing rodents humans, challenging can serve as sensitive surrogate for load; contribution becomes significant only very large loads. These findings important corollary anti-VEGF therapies sufficiently dosed avoid diversion by host-derived VEGF. further show our assay indicate when optimally blocked; do not exist other agents. Based on this assay, doses currently being assessed trials efficacious range.