High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model.
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.
Innovascreen Inc., 1959 Upper Water St. Suite 1700, Halifax, NS, B3J 3N2, Canada.|University of Alberta, 114th Street &87th Avenue, Edmonton, AB, T6G 2E1, Canada.
Desmond
D
Pink
Peregrine Pharmaceuticals Inc., 14282 Franklin Avenue Tustin, CA, 92780, USA.
Keith A
KA
Luhrs
Peregrine Pharmaceuticals Inc., 14282 Franklin Avenue Tustin, CA, 92780, USA.
Longen
L
Zhou
Innovascreen Inc., 1959 Upper Water St. Suite 1700, Halifax, NS, B3J 3N2, Canada.
Wendy
W
Schulte
Innovascreen Inc., 1959 Upper Water St. Suite 1700, Halifax, NS, B3J 3N2, Canada.
Jennifer
J
Chase
BioBroker, Arnold-Sommerfeld-Ring 2, 52499 Baesweiler, Germany.
Christian
C
Frosch
BioBroker, Arnold-Sommerfeld-Ring 2, 52499 Baesweiler, Germany.
Udo
U
Haberl
Peregrine Pharmaceuticals Inc., 14282 Franklin Avenue Tustin, CA, 92780, USA.
Van
V
Nguyen
Peregrine Pharmaceuticals Inc., 14282 Franklin Avenue Tustin, CA, 92780, USA.
Aparna I
AI
Roy
Innovascreen Inc., 1959 Upper Water St. Suite 1700, Halifax, NS, B3J 3N2, Canada.|University of Alberta, 114th Street &87th Avenue, Edmonton, AB, T6G 2E1, Canada.
John D
JD
Lewis
Innovascreen Inc., 1959 Upper Water St. Suite 1700, Halifax, NS, B3J 3N2, Canada.|Vanderbilt University Medical Center, 1161 21st Ave. S., Nashville, TN, 37232, USA.
Andries
A
Zijlstra
Peregrine Pharmaceuticals Inc., 14282 Franklin Avenue Tustin, CA, 92780, USA.
Missag H
MH
Parseghian
D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D051379:Mice
D000970:Antineoplastic Agents