Advancing Humanized Monoclonal Antibody for Counteracting Fentanyl Toxicity Towards Clinical Development

Overview

Journal Hum Vaccin Immunother

Specialty Allergy & Immunology

Date 2022 Oct 4

PMID 36194773

Authors

Dustin Hicks

Carly Baehr

Pedro Silva-Ortiz

Aaron Khaimraj

Diego Luengas

Fatima A Hamid

Marco Pravetoni

Affiliations

Soon will be listed here.

Abstract

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 and 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.

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