title: 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.
authors.affiliation: Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, D-82372 Penzberg, Germany. ulrich.weidle@roche.com.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Weidle
authors.forename: Georg
authors.initials: G
authors.lastname: Tiefenthaler
authors.forename: Christian
authors.initials: C
authors.lastname: Schiller
authors.forename: Elisabeth H
authors.initials: EH
authors.lastname: Weiss
authors.forename: Guy
authors.initials: G
authors.lastname: Georges
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brinkmann
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy*; D010940:Plant Proteins / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D000922:Immunotoxins; D010940:Plant Proteins
keywords: Anthrax toxin; deimmunization; diphthamide; diphtheria toxin; eukaryotic elongation factor 2; proof-of-concept studies; pseudomonas exotoxin; review; ribosome inactivating proteins; ricin; saporin