Prospects of bacterial and plant protein-based immunotoxins for treatment of cancer

Abstract

Bacterial- and plant-derived immunotoxins have documented potential for treatment of cancer. We discuss Anthrax toxin, ribosome inactivating-toxins, such as saporin and ricin, and ADP-ribosylating toxins such as Diphtheria toxin and Pseudomonas exotoxin, with focus on the latter, which has been most thoroughly investigated. Regarding their potential as anticancer agents, critical issues such as immunogenicity and toxicity are outlined. We describe different generations of immunotoxins, the pathways for the delivery of the cytotoxic 'warheads', molecular parameters modulating efficacy, and combination therapy with other anticancer agents. Finally, we discuss deimmunization strategies based on the removal of B- and T-cell epitopes from the cytotoxic component, and highlight promising clinical proof-of-concept studies.

Keywords: Anthrax toxin; deimmunization; diphthamide; diphtheria toxin; eukaryotic elongation factor 2; proof-of-concept studies; pseudomonas exotoxin; review; ribosome inactivating proteins; ricin; saporin.