[Immobilization of streptavidin-tagged bioactive hTNF-alpha on biotinylated mucosal surface of the bladder wall for treatment of superficial bladder cancer in mice].

Abstract

OBJECTIVE:

To investigate a novel immunotherapy through immobilization of streptavidin-tagged hTNF-alpha on the biotinylated mucosal surface of the bladder wall for bladder cancer treatment in mice.

METHODS:

A total of 120 female C57BL/6j mice were randomized into 5 equal groups, namely blank control, PBS, soluble hTNF-alpha, SA-GFP, and SA-hTNF-alpha treatment groups. Twenty-four hours after establishment of a mouse model of orthotopic superficial bladder cancer, SA-hTNF-alpha fusion protein was immobilized on the biotinylated mucosal surface of the bladder wall, which was repeated every 4 days for a total of 6 sessions. Immunohistochemistry was performed to detect the retention time of SA-hTNF-alpha fusion protein in the biotinylated mouse bladder mucosa and the distribution of CD4(+) and CD8(+) lymphocytes in the mucosa and tumor tissues, with the tumor growth and mouse survival also observed. The cytotoxiciy of the tumor-specific lymphocytes was evaluated. The mice responding well to the treatment were re-challenged by MB49 and monitored for survival.

RESULTS:

SA-hTNF-alpha could be efficiently and stably immobilized on the bladder mucosal surface for as long as 7 days. On day 60 after MB49 implantation, 18 out of 22 SA- hTNF-alpha-treated mice survived, with 9 appearing tumor-free, but all the mice in PBS control group died. Five out of 9 tumor-free mice in SA-hTNF-alpha group showed resistance to a re-challenge with intravesical MB49. The numbers of CD4(+) and CD8(+) lymphocytes were significantly greater in SA-hTNF-alpha group than in the other groups (P<0.05). The cytotoxicity of the tumor-specific lymphocytes was significantly stronger in SA-hTNF-alpha group than in the other groups (P<0.05).

CONCLUSION:

SA-hTNF-alpha immobilized on the biotinylated mucosal surface of the bladder wall can significantly inhibit the tumor growth and promote the survival of the mice bearing orthotopic superficial bladder cancer.

• Authors: Zhong Chen, Wan-long Tan, Xin Huang, Zhong-kun Liang, Cui-xiang Xu, Ji-min Gao
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 30 Issue 5 Pg. 936-40 (May 2010) ISSN: 1673-4254 [Print] China
• PMID: 20501361 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immobilized Proteins
• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha
• Streptavidin

Topics

• Administration, Intravesical
• Animals
• Biotinylation
• Carcinoma, Transitional Cell (immunology, therapy)
• Female
• Immobilized Proteins (therapeutic use)
• Immunotherapy (methods)
• Mice
• Mice, Inbred C57BL
• Recombinant Fusion Proteins (metabolism, therapeutic use)
• Streptavidin (metabolism, therapeutic use)
• Tumor Necrosis Factor-alpha (metabolism, therapeutic use)
• Urinary Bladder Neoplasms (immunology, therapy)