Immobilization of streptavidin-tagged bioactive hTNF-alpha on biotinylated mucosal surface of the bladder wall for treatment of superficial bladder cancer in mice.
- Author:
Zhong CHEN
1
;
Wan-long TAN
;
Xin HUANG
;
Zhong-kun LIANG
;
Cui-xiang XU
;
Ji-min GAO
Author Information
- Publication Type:Journal Article
- MeSH: 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
- From: Journal of Southern Medical University 2010;30(5):936-940
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSA 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.
RESULTSSA-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).
CONCLUSIONSA-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.