Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based on Pseudomonas exotoxin A.

ABSTRACT: Furin is a mammalian serine protease with important roles in cellular homeostasis and disease. It cleaves and activates numerous endogenous and exogenous substrates, including the SARS-CoV-2 viral spike protein and protein toxins such as diphtheria toxin and Pseudomonas exotoxin A (PE). Recombinant immunotoxins (RITs) are toxin conjugates used as cancer therapeutics that connect tumor-directed antibodies with toxins for targeted cell killing. RITs based on PE have shown success in treating a variety of cancers, but often suffer from safety and efficacy concerns when used clinically. We have explored furin as a potential limiting factor in the intoxication pathway of PE-based RITs. Although the furin has widely recognized importance in RIT intoxication, its role is incompletely understood.

SUBMITTER: Grossman BD 

PROVIDER: S-EPMC12208400 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature