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Rational design of an EGF-IL18 fusion protein: implication for developing tumor therapeutics.

Abstract：

:Interleukin-18 (IL-18) is a proinflammatory cytokine. This protein has a role in regulating immune responses and exhibits significant anti-tumor activities. Epidermal growth factor (EGF) is an important growth factor that plays a central role in the regulation of cell cycle and differentiation. It was proposed that a targeted delivery of IL-18 by generation of IL-18-EGF fusion protein might decrease adverse effects and result in enhancing cytotoxic and antitumor activities. In the present study, a fusion protein, consisting of EGFR binding domain fused to human IL-18 mature peptide via a linker peptide of (Gly(4)Ser) 3, was constructed and expressed in the insect cell line Sf9 using Bac-to-Bac baculovirus expression system. We showed that the purified recombinant fusion protein induced similar levels of IFN-gamma to that of native IL-18 protein in human PBMC in the presence of ConA. Furthermore, EGF receptor competitive test in human epithelial cancer A431 cell line showed that EGF-IL18 fusion protein can specifically bind with EGFR by competing with native EGF protein. These suggest that this rationally designed protein can be further developed as novel tumor therapeutics.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Lu JX,Peng Y,Meng ZF,Jin LQ,Lu YS,Guan MX

doi

10.1016/j.bbrc.2005.06.076

subject

Has Abstract

pub_date

2005-08-19 00:00:00

pages

157-61

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)01267-2

journal_volume

334

pub_type

杂志文章

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