Abstract
The majority of clinical trials with immunotoxins (ITs) have been conducted with conjugates containing ricin A-chain (Amlot et al. 1993; Grossbard et al. 1992; Vitetta et al. 1991). This has arisen largely as an historical accident simply because the early development of ITs was carried out with ricin as the toxin of choice, for no better reason than its availability. Native ricin poses a major handling hazard requiring special precautions. This is so because ricin is comprised of two chains, an A-chain which possesses the catalytic ribosome inactivating activity and a B-chain which has a lectin-like activity binding to galactose on the cell surface and it is this which confers nonspecific binding and hence toxicity to the intact toxin. Both the A- and B-chains of ricin are glycosylated, which confers liver binding properties that significantly contribute to their hepatotoxicity when used in patients. Saporin, by contrast, is a single chain, ribosome inactivating protein (rip) which consequently has no lectin-like binding activity and moreover is not glycosylated in the native form (Stirpe et al. 1983). Saporin is therefore very considerably safer to handle and can be used in its native form without the attendant toxicities associated with unmodified ricin based ilnmunoconjugates. The seeds of the soapwort plant (Saponaria officinalis) are a rich source of saporin and constitutes almost half a percent of the total weight of the seed. The gene for the SO6 isoform of saporin has been cloned and expressed in bacteria (Barthelemy et al. 1993). Saporin, like ricin A-chain, acts as an N-glycosidase catalytically cleaving 28S ribosomal RNA at A-4324 thus irreversibly inactivating cellular ribosome capability (Endo 1988). Despite the fact that saporin and ricin A-chain possess exactly the same catalytic activity and are compareble in their potency, the two proteins are antigenically unrelated.
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© 1998 Springer-Verlag Berlin Heidelberg
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Flavell, D.J. (1998). Saporin Immunotoxins. In: Frankel, A.E. (eds) Clinical Applications of Immunotoxins. Current Topics in Microbiology and Immunology, vol 234. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-72153-3_4
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DOI: https://doi.org/10.1007/978-3-642-72153-3_4
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