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Department of Experimental, Diagnostic and Specialty Medicine-DIMES; Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy





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Abstract Thirty years ago, the type 1 ribosome-inactivating protein RIP saporin-S6 also known as saporin was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials. View Full-Text

Keywords: saporin-S6; saporin; Saponaria officinalis; immunotoxin; immunotherapy; ribosome-inactivating proteins; monoclonal antibodies; rRNA N-glycosylase activity; anti-cancer therapy; hematological tumors saporin-S6; saporin; Saponaria officinalis; immunotoxin; immunotherapy; ribosome-inactivating proteins; monoclonal antibodies; rRNA N-glycosylase activity; anti-cancer therapy; hematological tumors





Autor: Letizia Polito * , Massimo Bortolotti, Daniele Mercatelli, Maria Giulia Battelli and Andrea Bolognesi

Fuente: http://mdpi.com/



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