Construction, expression and targeting therapeutic of single-chain immunotoxin against hepatocellular carcinoma.
- Author:
Jing ZHANG
1
;
Yan-fang LIU
;
Shou-jing YANG
;
Qing QIAO
;
Hong CHENG
;
Fu-cheng MA
;
Wan-lu CHEN
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Immunoglobulin Fragments; therapeutic use; Immunohistochemistry; Immunotoxins; therapeutic use; Liver Neoplasms, Experimental; therapy; Mice; Mice, Inbred BALB C; Tumor Necrosis Factor-alpha; therapeutic use
- From: Chinese Journal of Hepatology 2004;12(3):148-150
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVESTo obtain high therapeutic effect and low toxicity single-chain immunotoxin against hepatocellular carcinoma (HCC).
METHODSHuman mutant tumor necrosis factor-alpha (mTNFalpha) was linked with the 3' end of humanized single-chain Fv against HCC (hscFv25) in pGEX4T-1 vector. The anti-HCC immunotoxin was expressed in Escherichia coli and identified by western blot. The primary tumor regression trial in nude mice bearing HCC was evaluated the targeting therapeutic value of hscFv25-mTNFalpha. The tumor tissues were stained by immunohistochemical with TNFalpha antibody.
RESULTSThe expression of single-chain immunotoxin hscFv25-mTNFalpha was 12% of total bacteria proteins. The tumor regression trials of hscFv25-mTNFalpha showed 5/5 effective. It had 2/5 completely remission and 3/5 partly remission. The therapeutic result of hscFv25-mTNFalpha was better than that of mTNFalpha (F=8.70, 0.05). The HCC tissue treated by hscFv25-mTNFalpha expressed TNFalpha positive reaction. The positive granule mainly existed in HCC cytoplasm.
CONCLUSIONThe single-chain immunotoxin hscFv25-mTNFalpha has high therapeutic effect and low toxicity. It has potentialities for clinical application.
