Monoclonal Antibodies Engineered with Fc Region Mutations to Extend Protection against Fentanyl Toxicity.

ABSTRACT: Fentanyl and other synthetic opioids are the leading cause of drug-related deaths in the United States. mAbs that selectively target fentanyl and fentanyl analogues offer a promising strategy for treating both opioid-related overdoses and opioid use disorders. To increase the duration of efficacy of a candidate mAb against fentanyl, we selected three sets of mutations in the Fc region of an IgG1 anti-fentanyl mAb (HY6-F9DF215, HY6-F9DHS, HY6-F9YTE) to increase binding to the neonatal Fc receptor (FcRn). The mAb mutants were compared against unmodified (wild-type [WT], HY6-F9WT) anti-fentanyl mAb for fentanyl binding, thermal stability, and FcRn affinity in vitro, and for efficacy against fentanyl and mAb half-life in vivo in mice. Biolayer interferometry showed a >10-fold increase in the a

SUBMITTER: Khaimraj A 

PROVIDER: S-EPMC11333160 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature