Plant-Derived Type I Ribosome Inactivating Protein-Based Targeted Toxins: A Review of the Clinical Experience

Abstract

Targeted toxins (TT) for cancer treatment are a class of hybrid biologic comprised of a targeting domain coupled chemically or genetically to a proteinaceous toxin payload. The targeting domain of the TT recognises and binds to a defined target molecule on the cancer cell surface, thereby delivering the toxin that is then required to internalise to an appropriate intracellular compartment in order to kill the target cancer cell. Toxins from several different sources have been investigated over the years, and the two TTs that have so far been licensed for clinical use in humans; both utilise bacterial toxins. Relatively few clinical studies have, however, been undertaken with TTs that utilise single-chain type I ribosome inactivating proteins (RIPs). This paper reviews the clinical experience that has so far been obtained for a range of TTs based on five different type I RIPs and concludes that the majority studied in early phase trials show significant clinical activity that justifies further clinical investigation. A range of practical issues relating to the further clinical development of TT’s are also covered briefly together with some suggested solutions to outstanding problems.