Title:Immunotoxins Constructed with Ribosome-Inactivating Proteins and their Enhancers: A Lethal Cocktail with Tumor Specific Efficacy
Volume: 20
Issue: 42
Author(s): Roger Gilabert-Oriol, Alexander Weng, Benedicta von Mallinckrodt, Matthias F. Melzig, Hendrik Fuchs and Mayank Thakur
Affiliation:
Keywords:
Targeted toxins, immunotoxins, ribosome-inactivating proteins, clinical application of toxins, tumor therapy, efficacy enhancer,
endosomal escape enhancer.
Abstract: The term ribosome-inactivating protein (RIP) is used to denominate proteins mostly of plant origin, which have N-glycosidase
enzymatic activity leading to a complete destruction of the ribosomal function. The discovery of the RIPs was almost a century ago, but
their usage has seen transition only in the last four decades. With the advent of antibody therapy, the RIPs have been a subject of extensive
research especially in targeted tumor therapies, which is the primary focus of this review. In the present work we enumerate 250
RIPs, which have been identified so far. An attempt has been made to identify all the RIPs that have been used for the construction of
immunotoxins, which are conjugates or fusion proteins of an antibody or ligand with a toxin. The data from 1960 onwards is reviewed in
this paper and an extensive list of more than 450 immunotoxins is reported. The clinical reach of tumor-targeted toxins has been identified
and detailed in the work as well. While there is a lot of potential that RIPs embrace for targeted tumor therapies, the success in preclinical
and clinical evaluations has been limited mainly because of their inability to escape the endo/lysosomal degradation. Various
strategies that can increase the efficacy and lower the required dose for targeted toxins have been compiled in this article. It is plausible
that with the advancements in platform technologies or improved endosomal escape the usage of tumor targeted RIPs would see the daylight
of clinical success.
