Modular Pore-Forming Immunotoxins with Caged Cytotoxicity Tailored by Directed Evolution.

ABSTRACT: Immunotoxins are proteins containing a cell-targeting element linked to a toxin that are under investigation for next-generation cancer treatment. However, these agents are difficult to synthesize, chemically heterogeneous, expensive, and show toxicity toward healthy cells. In this work, we describe the synthesis and characterization of a new type of immunotoxin that showed exquisite selectivity toward targeted cells. In our construct, targeting molecules were covalently attached or genetically fused to oligomeric pore-forming toxins. The activity of the immunotoxin was then caged by fusing a soluble protein to the transmembrane domain and activated via cleavage with furin, which is a protease that is overexpressed in many cancer cells. During the several coupling steps, directed evolution

SUBMITTER: Mutter NL 

PROVIDER: S-EPMC6243392 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature