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.

Immunotoxins: The Role of the Toxin

“…These include modulating immune responses: such as preventing graft versus host disease [33,34], removing T-cells from grafts [35,36] or the elimination T-regulatory cells [37,38,39,40]. Some progress has been made also in producing immunotoxins with anti-viral [41,42,43] or anti-parasitic activity [44]. Ex-vivo uses are also anticipated whereby unwanted cells are killed before infusing bone marrow or other stem cell like preparations [45,46].…”

Anti-profibrotic effects of artesunate on bleomycin-induced pulmonary fibrosis in Sprague Dawley rats

“…Notably, a previous study demonstrated that artesunate conjugated with a single-chain variable fragment from the monoclonal antibody NP11-4 inhibited liver fibrosis induced by schistosomiasis (14). Therefore, it was hypothesized that artesunate may attenuate pulmonary fibrosis.…”

“…Hydroxyproline content in the four groups at different time points (µg/g) At 7,14,21. and 28 days after bleomycin injection with or without artesunate treatment, rats were exsanguinated and their lungs were removed.…”

Artesunate Inhibits the Development of PVR by Supreesing TGF-β/Smad Signaling Passway

“…Artesunate is a kind of artemisinin derivatives, which is a traditional Chinese medicine widely used as anti malaria drugs.Artesunate has good water solubility and high oral bioavailability, so it has good pharmacological effect [11].Recent studies have found that,Artemisinin, a long-term anti malaria drug, has been proved to have antioxidant, anti-in ammatory, anti apoptotic and anti proliferative effects, making it a therapeutic option for eye diseases [11,12].Studies have shown that artesunate can inhibit the proliferation of human ovarian cancer cells and TGF-β [13].However, its preventive effect on RPE cells is not clear.…”