Prospects of Bacterial and Plant Protein-based Immunotoxins for Treatment of Cancer

Cancer Genomics - Proteomics

CHRISTIAN SCHILLER¹  GEORG TIEFENTHALER²  ELISABETH H. WEISS¹  ULRICH H. WEIDLE²  GUY GEORGES²  ULRICH BRINKMANN² 

[1] Department of Biology II, Ludwig Maximilians University, Munich, Germany Department of Biology II, Ludwig Maximilians University, Munich, Germany Department of Biology II, Ludwig Maximilians University, Munich, Germany;Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, Penzberg, Germany Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, Penzberg, Germany Roche Pharma Research and Early Development (pRED), Roche Diagnostics GmbH, Penzberg, Germany

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

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

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.

【 授权许可】

Unknown