Innovative therapies to complement current treatments are needed to curb the growing incidence of fatal overdoses related to synthetic opioids. Murine and chimeric monoclonal antibodies (mAb) specific for fentanyl and its analogs have demonstrated pre-clinical efficacy in preventing and reversing drug-induced toxicity in rodent models. However, mAb-based therapeutics require extensive engineering as well as in vitro and in vivo characterization to advance to first-in-human clinical trials. Here, novel murine anti-fentanyl mAbs were selected for development based on affinity for fentanyl, and efficacy in counteracting the pharmacological effects of fentanyl in mice. Humanization and evaluation of mutations designed to eliminate predicted post-translational modifications resulted in two humanized mAbs that were effective at preventing fentanyl-induced pharmacological effects in rats. These humanized mAbs showed favorable biophysical properties with respect to aggregation and hydrophobicity by chromatography-based assays, and thermostability by dynamic scanning fluorimetry. These results collectively support that the humanized anti-fentanyl mAbs developed herein warrant further clinical development for treatment of fentanyl toxicity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.