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High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model.

ABSTRACT: The use of rodent models to evaluate efficacy during testing is accompanied by significant economic and regulatory hurdles which compound the costs of screening for promising drug candidates. Vasopermeation Enhancement Agents (VEAs) are a new class of biologics that are designed to increase the uptake of cancer therapeutics at the tumor site by modifying vascular permeability in the tumor to increase the therapeutic index of co-administered drugs. To evaluate the efficacy of a panel of VEA clinical candidates, we compared the rodent Miles assay to an equivalent assay in the ex ovo chicken embryo model. Both model systems identified the same candidate (PVL 10) as the most active promoter of vasopermeation in non-tumor tissues. An ex ovo chicken embryo system was utilized to test each candidate VEA in two human tumor models at a range of concentrations. Vasopermeation activity due to VEA was dependent on tumor type, with HEp3 tumors displaying higher levels of vasopermeation than MDA-MB-435. One candidate (PVL 10) proved optimal for HEp3 tumors and another (PVL 2) for MDA-MB-435. The use of the ex ovo chicken embryo model provides a rapid and less costly alternative to the use of rodent models for preclinical screening of drug candidates.

SUBMITTER: Pink D

PROVIDER: S-EPMC4625159 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model.

Pink Desmond D Luhrs Keith A KA Zhou Longen L Schulte Wendy W Chase Jennifer J Frosch Christian C Haberl Udo U Nguyen Van V Roy Aparna I AI Lewis John D JD Zijlstra Andries A Parseghian Missag H MH

Scientific reports 20151029

The use of rodent models to evaluate efficacy during testing is accompanied by significant economic and regulatory hurdles which compound the costs of screening for promising drug candidates. Vasopermeation Enhancement Agents (VEAs) are a new class of biologics that are designed to increase the uptake of cancer therapeutics at the tumor site by modifying vascular permeability in the tumor to increase the therapeutic index of co-administered drugs. To evaluate the efficacy of a panel of VEA clini ...[more]

PMID: 26510887

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High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model.

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High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model.

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