:: Volume 21, Number 2 (3-2017) ::
IBJ 2017, 21(2): 77-83 Back to browse issues page
Evaluation of an Albumin-Binding Domain Protein Fused to Recombinant Human IL-2 and Its Effects on the Bioactivity and Serum Half-Life of the Cytokine
Elham Adabi, Fateme Saebi, Amin Moradi Hasan-Abad, Ladan Teimoori-Toolabi, Gholam Ali Kardar
Abstract:  

Background: Cancer immunotherapy is a promising strategy for cancer treatment. In this strategy,   the immune system is triggered to destroy cancer cells. IL-2 is an important factor in passive cancer immunotherapy that helps modulating some important immune functions. One of the IL-2 limitations is low serum half-life; therefore, repetitive high doses of the injections are required to maintain effective concentrations. High-dose IL-2 therapy results in severe side effects; thus, improvement of its serum half-life would provide therapeutic benefits. Methods: We have investigated a strategy that is able to utilize an albumin-binding domain (ABD) from streptococcal protein G. In this strategy, the fusion protein ABD-rIL-2 binds to serum albumin, which results in improvement of the IL-2 serum half-life. PET26b+ plasmid was used as an expression vector, which encoded rIL-2 and ABD-rIL-2 both fused to pelB secretion signal under the control of the strong bacteriophage T7 promoter. The constructs were expressed in E. coli Rosetta (DE3) and secreted into the periplasm. Results: The analysis of in vitro bioactivity proved that the fusion of ABD to rIL-2 does not interfere with its bioactivity. ABD-rIL-2 fusion protein indicated higher serum half-life compared to rIL-2, when it was tested in the BALB/c mice. Conclusion: The current study provides an alternative strategy to extend the half-life and improve pharmacokinetic properties of rIL-2 without reducing its bioactivity in vitro.

Keywords: Albumin, Albumin-binding domain, Bioactivity, Fusion protein, Interleukin 2, Pharmacokinetics, Serum half-life
Full-Text [PDF 850 kb]      
Type of Study: Full Length | Subject: Medical Biotechnology
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DOI: 10.18869/acadpub.ibj.21.2.77
PMID: 27805072
PMCID: PMC5274714


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Adabi E, Saebi F, Moradi Hasan-Abad A, Teimoori-Toolabi L, Kardar G A. Evaluation of an Albumin-Binding Domain Protein Fused to Recombinant Human IL-2 and Its Effects on the Bioactivity and Serum Half-Life of the Cytokine. IBJ. 2017; 21 (2) :77-83
URL: http://ibj.pasteur.ac.ir/article-1-1849-en.html
Volume 21, Number 2 (3-2017) Back to browse issues page
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