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Modified DT-IL2 fusion toxin targeting uniquely IL2Rα expressing leukemia cell lines - Construction and characterization
Published in
2010
PMID: 20580754
Volume: 148
   
Issue: 2-3
Pages: 147 - 155
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. © 2010 Elsevier B.V.
About the journal
JournalJournal of Biotechnology
ISSN01681656
Open AccessNo
Concepts (53)
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    After-treatment
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    Cell lines
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    Cell viability
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    CYTOTOXIC ACTIVITIES
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    Diphtheria toxin
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    FUSION PROTEINS
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    FUSION TOXINS
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    HIGH AFFINITY
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    IMMUNOTOXINS
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    INTERLEUKIN-2
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    LEUKEMIA CELLS
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    NEGATIVE CONTROL
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    NEGATIVE CORRELATION
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    SELECTIVE LIGANDS
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    Tumor cells
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    Amino acids
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    Cell culture
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    Ligands
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    Metabolites
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    Organic acids
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    Proteins
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    Toxic materials
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    DENILEUKIN DIFTITOX
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    IMMUNOTOXIN
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    IMMUNOTOXIN SPRSV1
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    IMMUNOTOXIN SPRSV2
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    IMMUNOTOXIN SPRSV3
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    IMMUNOTOXIN SPRSV4
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    INTERLEUKIN 2
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    INTERLEUKIN 2 RECEPTOR ALPHA
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    Unclassified drug
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    Article
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    Controlled study
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    Cytotoxicity
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    Human
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    Human cell
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    LEUKEMIA CELL LINE
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    Priority journal
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    Apoptosis
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    Blotting, western
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    Cell line, tumor
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    Cell proliferation
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    Cell survival
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    Drug delivery systems
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    Electrophoresis, polyacrylamide gel
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    Flow cytometry
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    Humans
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    IMMUNOTOXINS
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    INTERLEUKIN-2
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    INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT
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    Leukemia
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    Microscopy
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    Recombinant fusion proteins