Saporin-S6: A Useful Tool in Cancer Therapy

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.

The thermal unfolding of the ribosome-inactivating protein saporin-S6 characterized by infrared spectroscopy

“…Among all RIPs, saporin-S6 is one of the most studied because of its strong activity both in cell-free systems and in cell lines and for their demonstrated numerous potential applications [11].…”

Optimization of construct design and fermentation strategy for the production of bioactive ATF-SAP, a saporin based anti-tumoral uPAR-targeted chimera

“…Among plant RIPs, saporin (SAP) is characterized by a high level of enzymatic activity, stability and resistance to conjugation procedures and blood proteases, that potentially make this toxin a very useful tool in cancer therapy. SAP-based ITs or LT fusions have been employed in preclinical studies with encouraging results and a few of them are under investigation in clinical trials [5]. Among the potential targets, a special place is deserved to the human urokinase-type plasminogen activator (uPA) and its receptor (uPAR) that have been demonstrated to be involved in the neoplastic evolution, including tumor cell proliferation, adhesion and migration, intravasation and extravasation, growth at the metastatic sites and tumor neo-angiogenesis.…”

Biotoxins for Cancer Therapy

“…Saporin-S6 (also known as saporin), first isolated from Saponaria officinalis L. seeds, is widely employed in the construction of conjugates and immunotoxins for different purposes. The immunotoxin has shown high enzymatic activity, stability and resistance to conjugation procedures and blood proteases when used in cancer therapy, particularly in hematological tumors, which make saporin-S6 a very useful tool in cancer therapy (Polito et al, 2013). Ricin toxin (RTB) from castor plant is used as a vaccine adjuvant/carrier to design cancer vaccines, since it has the most effective immunogens.…”