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Toxins 2017, 9(6), 182; doi:10.3390/toxins9060182

Two Saporin-Containing Immunotoxins Specific for CD20 and CD22 Show Different Behavior in Killing Lymphoma Cells

Department of Experimental, Diagnostic and Specialty Medicine—DIMES, General Pathology Section, Alma Mater Studiorum—University of Bologna, Via S. Giacomo 14, 40126 Bologna, Italy
These authors contributed equally to this work.
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Academic Editors: Daniel Gillet and Julien Barbier
Received: 12 April 2017 / Revised: 18 May 2017 / Accepted: 26 May 2017 / Published: 30 May 2017
(This article belongs to the Special Issue Ribosome Inactivating Toxins)
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Abstract

Immunotoxins (ITs) are hybrid proteins combining the binding specificity of antibodies with the cytocidal properties of toxins. They represent a promising approach to lymphoma therapy. The cytotoxicity of two immunotoxins obtained by chemical conjugation of the plant toxin saporin-S6 with the anti-CD20 chimeric antibody rituximab and the anti-CD22 murine antibody OM124 were evaluated on the CD20-/CD22-positive cell line Raji. Both ITs showed strong cytotoxicity for Raji cells, but the anti-CD22 IT was two logs more efficient in killing, probably because of its faster internalization. The anti-CD22 IT gave slower but greater caspase activation than the anti-CD20 IT. The cytotoxic effect of both immunotoxins can be partially prevented by either the pan-caspase inhibitor Z-VAD or the necroptosis inhibitor necrostatin-1. Oxidative stress seems to be involved in the cell killing activity of anti-CD20 IT, as demonstrated by the protective role of the H2O2 scavenger catalase, but not in that of anti-CD22 IT. Moreover, the IT toxicity can be augmented by the contemporary administration of other chemotherapeutic drugs, such as PS-341, MG-132, and fludarabine. These results contribute to the understanding of the immunotoxin mechanism of action that is required for their clinical use, either alone or in combination with other drugs. View Full-Text
Keywords: B-lymphoma; CD20; CD22; immunotherapy; immunotoxin; ribosome-inactivating proteins; saporin-S6 B-lymphoma; CD20; CD22; immunotherapy; immunotoxin; ribosome-inactivating proteins; saporin-S6
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MDPI and ACS Style

Polito, L.; Mercatelli, D.; Bortolotti, M.; Maiello, S.; Djemil, A.; Battelli, M.G.; Bolognesi, A. Two Saporin-Containing Immunotoxins Specific for CD20 and CD22 Show Different Behavior in Killing Lymphoma Cells. Toxins 2017, 9, 182.

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