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Modified DT–IL2 fusion toxin targeting uniquely IL2Rα expressing leukemia cell lines – Construction and characterization

Paper ID Volume ID Publish Year Pages File Format Full-Text
24094 43496 2010 9 PDF Available
Title
Modified DT–IL2 fusion toxin targeting uniquely IL2Rα expressing leukemia cell lines – Construction and characterization
Abstract

Immunotoxins are fusion proteins of modified toxin conjugated to tumor cell selective ligand. Denileukin diftitox approved by FDA for treatment of CTCL is diphtheria toxin (DT)/IL2 fusion protein targeted to high affinity IL2R. Here, we have attempted to target the more uniquely expressed low affinity IL2R (IL2Rα). We designed four immunotoxins, SPRSV1 was designed to code for a single protein of DT (390) and IL2 (133) without any extra amino acids at the junction. SPRSV2 was designed to selectively target low affinity IL2R, it codes for DT (390) and IL2 (69). We also constructed SPRSV3 encoding for only DT (390) without any ligand, as negative control and SPRSV4 was designed similar to commercial equivalent denileukin diftitox, it codes for DT (387) and IL2 (133) with His at the junction. The cytotoxic activities of these immunotoxins were tested in various cell lines, cell lines lacking IL2R expression and healthy MNC were used as controls. The activities of SPRSV1 and SPRSV2 were comparable to that of SPRSV4. SPRSV2 exhibited potent cytotoxicity effectively targeted to α subunit of IL2R on various leukemia cell lines. Our studies also showed a negative correlation between CD25 expression and percentage cell viability after treatment with immunotoxins.

Keywords
Diphtheria toxin; Interleukin-2; Interleukin-2 receptor; Immunotoxins; Fusion toxins
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Modified DT–IL2 fusion toxin targeting uniquely IL2Rα expressing leukemia cell lines – Construction and characterization
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Biotechnology - Volume 148, Issues 2–3, 20 July 2010, Pages 147–155
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us