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Toxins 2018, 10(2), 82; https://doi.org/10.3390/toxins10020082

Strategies to Improve the Clinical Utility of Saporin-Based Targeted Toxins

1
Department of Life, Health and Environmental Sciences, University of L’Aquila, I-67100 L’Aquila, Italy
2
The Simon Flavell Leukaemia Research Laboratory (Leukaemia Busters), Southampton General Hospital, Southampton, SO16 8AT, UK
3
Italian Ministry of Education, I-20100 Milano, Italy
*
Author to whom correspondence should be addressed.
Received: 16 December 2017 / Revised: 29 January 2018 / Accepted: 11 February 2018 / Published: 13 February 2018
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Abstract

Plant Ribosome-inactivating proteins (RIPs) including the type I RIP Saporin have been used for the construction of Immunotoxins (ITxs) obtained via chemical conjugation of the toxic domain to whole antibodies or by generating genetic fusions to antibody fragments/targeting domains able to direct the chimeric toxin against a desired sub-population of cancer cells. The high enzymatic activity, stability and resistance to conjugation procedures and especially the possibility to express recombinant fusions in yeast, make Saporin a well-suited tool for anti-cancer therapy approaches. Previous clinical work on RIPs-based Immunotoxins (including Saporin) has shown that several critical issues must be taken into deeper consideration to fully exploit their therapeutic potential. This review focuses on possible combinatorial strategies (chemical and genetic) to augment Saporin-targeted toxin efficacy. Combinatorial approaches may facilitate RIP escape into the cytosolic compartment (where target ribosomes are), while genetic manipulations may minimize potential adverse effects such as vascular-leak syndrome or may identify T/B cell epitopes in order to decrease the immunogenicity following similar strategies as those used in the case of bacterial toxins such as Pseudomonas Exotoxin A or as for Type I RIP Bouganin. This review will further focus on strategies to improve recombinant production of Saporin-based chimeric toxins. View Full-Text
Keywords: Saponaria officinalis; immunotherapy; ribosome-inactivating proteins; monoclonal antibodies; anti-cancer therapy; chimeric toxin Saponaria officinalis; immunotherapy; ribosome-inactivating proteins; monoclonal antibodies; anti-cancer therapy; chimeric toxin
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Giansanti, F.; Flavell, D.J.; Angelucci, F.; Fabbrini, M.S.; Ippoliti, R. Strategies to Improve the Clinical Utility of Saporin-Based Targeted Toxins. Toxins 2018, 10, 82.

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