title: The efficacy of NP11-4-derived immunotoxin scFv-artesunate in reducing hepatic fibrosis induced by Schistosoma japonicum in mice.
abstract: Schistosomiasis is one of the most prevalent parasitic diseases in China, and hepatic fibrosis caused by schistosome infection is the principal cause of death. The aim of this study was to evaluate the efficacy of NP11-4-derived immunotoxin scFv-artesunate on Schistosoma japonicum-induced hepatic fibrosis. A single-chain variable fragment (scFv) was generated from the murine anti-Schistosoma japonicum (S. japanicum) monoclonal antibody NP11-4. The scFv was expressed as a soluble protein and purified by Ni-affinity chromatography. After conjugation with artesunate, the binding ability with soluble egg antigens (SEA) was determined by an enzyme-linked immunosorbent assay (ELISA). The biological activity of purified scFv, scFv-artesunate (immunotoxin), and artesunate was detected in vivo. Image-Pro Plus software was used to analyze the size of egg granuloma and the extent of liver fibrosis. The recombinant scFv expession vector was constructed and expressed successfully. After purification by a His-trap Ni-affinity column, the scFv yield was approximately 0.8 mg/L of culture medium. ELISA results showed that chemical conjugation did not affect the binding activity of the immunotoxin. Our animal experiments indicated that the immunotoxin could significantly reduce the size of egg granuloma in the liver and inhibit hepatic fibrosis. The immunotoxin could be used as a promising candidate in the targeted therapy of S. japonicum-induced hepatic fibrosis.
authors.affiliation: Key Labortary of Antibody Technique of Ministry of Health, Nanjing Medical University, Nanjing, Jiangsu 210029, China ; Pathology Department, Nanjing Medical University, Nanjing, Jiangsu 210029, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Chunyan
authors.initials: C
authors.lastname: Gu
authors.forename: Yongya
authors.initials: Y
authors.lastname: Ren
authors.forename: Yang
authors.initials: Y
authors.lastname: Dai
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: Zhenning
authors.initials: Z
authors.lastname: Qiu
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Yinchang
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Guan
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Feng
keywords: Schistosoma japonicum; hepatic fibrosis; immunotoxin; scFv
references.citation: Cancer Res. 1992 Jun 15;52(12):3402-8
references.pmid: 1596900
references.citation: Acta Trop. 2005 Nov-Dec;96(2-3):106-16
references.pmid: 16168945
references.citation: J Biochem. 1999 Feb;125(2):328-33
references.pmid: 9990130
references.citation: Mem Inst Oswaldo Cruz. 2000 May-Jun;95(3):375-80
references.pmid: 10800196
references.citation: Int J Med Microbiol. 2004 Apr;293(7-8):577-82
references.pmid: 15149034
references.citation: Chin Med J (Engl). 2001 Jul;114(7):772
references.pmid: 11780349
references.citation: Exp Parasitol. 2009 Aug;122(4):310-7
references.pmid: 19389399
references.citation: J Gastroenterol Hepatol. 2010 Jul;25(7):1266-75
references.pmid: 20594254
references.citation: Exp Parasitol. 2009 Aug;122(4):344-8
references.pmid: 19371743
references.citation: Clin Microbiol Rev. 2010 Apr;23(2):442-66
references.pmid: 20375361
references.citation: Acta Trop. 2005 Nov-Dec;96(2-3):168-76
references.pmid: 16125657
references.citation: Expert Opin Biol Ther. 2004 Jul;4(7):1115-28
references.pmid: 15268678
references.citation: J Egypt Soc Parasitol. 1994 Dec;24(3):685-95
references.pmid: 7844435
references.citation: Mem Inst Oswaldo Cruz. 1998;93 Suppl 1:267-8
references.pmid: 9921366
references.citation: Emerg Infect Dis. 2007 Oct;13(10):1470-6
references.pmid: 18257989
references.citation: Acta Biochim Biophys Sin (Shanghai). 2010 Feb;42(2):129-36
references.pmid: 20119624
references.citation: N Engl J Med. 2002 Apr 18;346(16):1212-20
references.pmid: 11961151
references.citation: Am J Trop Med Hyg. 1994 Jul;51(1):83-8
references.pmid: 8059919
references.citation: Parasitol Int. 2003 Dec;52(4):341-9
references.pmid: 14665392
references.citation: Cancer Gene Ther. 2002 Nov;9(11):884-96
references.pmid: 12386827
references.citation: Anticancer Res. 2010 Sep;30(9):3373-9
references.pmid: 20944111
references.citation: Int J Cancer. 2011 Jul 1;129(1):111-21
references.pmid: 20824708
references.citation: Intern Med. 2010;49(11):1001-5
references.pmid: 20519816
references.citation: Int J Parasitol. 2009 Jan;39(2):191-200
references.pmid: 18804475
references.citation: Acta Trop. 2005 Nov-Dec;96(2-3):69-96
references.pmid: 16312039
references.citation: Protein Eng. 1994 Aug;7(8):1027-33
references.pmid: 7809029
references.citation: Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2011 Dec;23(6):599-604
references.pmid: 22379811
references.citation: Protein Expr Purif. 2003 Jan;27(1):85-9
references.pmid: 12509988
references.citation: Parasitol Today. 2000 Mar;16(3):122-6
references.pmid: 10689333
references.citation: Curr Opin Urol. 2001 Jan;11(1):97-101
references.pmid: 11148754
references.citation: Mol Med Today. 1996 Oct;2(10):439-46
references.pmid: 8897439
references.citation: Parasitol Res. 2009 Apr;104(5):955-65
references.pmid: 19255786