IL2 fused to lectin-deficient ricin is toxic to human leukemia cells expressing the IL2 receptor

Leukemia
A E FrankelE Tagge

Abstract

Interleukin-2 (IL2) fused to ricin B chain (RTB) with modifications of amino acid residues in each of three galactose-binding subdomains (1alpha, 1beta and 2gamma) was expressed in insect cells, purified by immunoaffinity chromatography and reassociated with ricin A chain (RTA). The fusion toxin-bound human leukemic cells with IL2 receptors and the binding was competed with IL2 but not asialofetuin. In contrast, binding was not observed with receptor negative human cell lines, and the fusion molecule very weakly bound asialofetuin (Kd= 10(-6)M), indicating lectin-deficient RTB. The IL2-lectin-deficient RTB-RTA intoxicated IL2 receptor bearing cells as well as ricin or IL2-wild-type RTB-RTA. While ricin and IL2-wild-type RTB-RTA were equally toxic to receptor negative cell lines, the IL2-lectin-deficient RTB-RTA was two-two and one half logs less cytotoxic to these cell lines. The sensitivity of receptor-positive cells to the lectin-deficient fusion protein suggests that high avidity intracellular galactose binding may not be required for ricin intoxication, at least in the case of IL2 receptor-targeted molecules. Furthermore, the potent selective cytotoxicity of the fusion protein suggests that the IL2-lectin-deficient RTB-RTA ...Continue Reading

Citations

Sep 7, 2012·Trends in Immunology·Ethan M Shevach
Feb 25, 2005·Vitamins and Hormones·Claudia M LitterstEdith Pfitzner
Nov 12, 2005·European Journal of Pediatrics·Heike PhilippiJuergen Spranger
Jun 5, 2013·Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion·Britta AuelUNKNOWN German Refractory Myeloma Study Group
Mar 4, 2003·The Journal of Biological Chemistry·Juliette Morlon-GuyotBruno Beaumelle

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