Primary targeting of recombinant Fv-immunotoxin hscFv25-mTNF&alpha; against hepatocellular carcinoma

doi:10.3748/wjg.v10.i13.1872

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Liver Cancer

World J Gastroenterol. Jul 1, 2004; 10(13): 1872-1875
Published online Jul 1, 2004. doi: 10.3748/wjg.v10.i13.1872

Primary targeting of recombinant Fv-immunotoxin hscFv₂₅-mTNFα against hepatocellular carcinoma

Jing Zhang, Yan-Fang Liu, Shou-Jing Yang, Qing Qiao, Hong Cheng, Chuan-Shan Zhang, Fu-Cheng Ma, Hua-Zhang Guo

Jing Zhang, Yan-Fang Liu, Shou-Jing Yang, Hong Cheng, Chuan-Shan Zhang, Fu-Cheng Ma, Hua-Zhang Guo, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an 710033, Shaanxi Province, China

Qing Qiao, Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province, China

Author contributions: All authors contributed equally to the work.

Supported by Military 95 Major Supplementary Project, No.98M098

Correspondence to: Jing Zhang, Department of Pathology, Xijing Hospital, Fourth Military Medical University, Xi’an 710033, Shaanxi Province, China. jzhang@fmmu.edu.cn

Telephone: +86-29-83375497 Fax: +86-29-83375497

Received: December 28, 2003
Revised: January 1, 2004
Accepted: January 8, 2004
Published online: July 1, 2004

Abstract

AIM: To obtain human recombinant Fv-immunotoxin hscFv₂₅-mTNFα (mutant human TNFα fused to human scFv₂₅) against hepatocellular carcinoma (HCC).

METHODS: Two relevant sites of enzymatic digestion were added to mTNFα by PCR. mTNFα was linked to the 3’ end of hscFv₂₅ in pGEX4T-1 vector. This anti-HCC recombinant Fv-immunotoxin hscFv₂₅-mTNFα was expressed in Escherichia coli and purified from inclusions. After purified by glutathione-S-transferase affinity chromatography and thrombin digestion, it was identified by electrophoresis and Western blot. And then, the purified recombinant Fv-immunotoxin was injected into nude mice with HCC xenografts through their tail veins. mTNFα protein and PBS were used as control at the same time. After treated for two weeks, nude mice were executed. The bulk and weight of tumors were observed. The tumor tissues were stained by immunohistochemical method with TNFα antibody.

RESULTS: The expression ratio of recombinant Fv-immunotoxin hscFv₂₅-mTNFα was 12% of bacterial protein. The result of tumor restraining trials of hscFv₂₅-mTNFα showed 2/5 complete remission and 3/5 partial remission. mTNFα restraining trials showed 5/5 partial remission. The therapeutic result of hscFv₂₅-mTNFα was better than that of mTNFα (F = 8.70, P < 0.05). The hscFv₂₅-mTNFα remedial tumor tissues were positive for TNFα by immunohistochemical staining. The positive granules mainly existed in the cytoplasm of tumor cell.

CONCLUSION: Recombinant Fv-immunotoxin hscFv₂₅-mTNFα has better therapeutic effect than mTNFα. It can inhibit the cellular growth of HCC and has some potential of clinical application.

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