SA-IL-2锚定修饰治疗表浅膀胱癌的实验研究(英文)  

A novel immunotherapy for superficial bladder cancer by the immobilization of streptavidin-tagged bioactive IL-2 on the biotinylated mucosal surface of the bladder wall

作　　者：黄鑫 余宏盛 陈忠 

机构地区：[1]Institute of Biotherapy,School of Biotechnology,Southern Medical University,Guangzhou [2]Zhejiang Provincial Key Laboratory of Medical Genetics,School of Life Sciences,Wenzhou Medical College [3]Department of Urologic Surgery in Nanfang Hospital,Southern Medical University

出　　处：《Chinese Journal of Cancer》2010年第6期611-616,共6页

基　　金：National 863 project (No. 2006AA02Z4C4 );Sci-Tech Research Project of Baiyun district,Guangzhou (No. 2009-SZ-40)

摘　　要：Background and Objective:Intravesical administration of Bacillus Calmette-Guèrin(BCG) after transurethral resection is by far the most effective local therapy for superficial bladder cancer,the fifth most common cancer in the world.However,approximately one-third of patients fail to respond and most patients eventually relapse.In addition,there are pronounced side effects of BCG therapy,such as BCG sepsis and a high frequency of BCG-induced cystitis.This study established a novel immunotherapy through immobilization of streptavidin-tagged human IL-2(SA-hIL-2) on the biotinylated mucosal surface of bladder wall.Methods:A mouse orthotopic model of MB49 bladder cancer was established by perfusing MB49 cells into mouse bladders.The SA-hIL-2 fusion protein was immobilized on the biotinylated mucosal surface of the bladder wall.Treatment began on day 1 after MB49 implantation,once every 3 days for 6 times.Immunohistochemical assay was performed to assess the persistence of SA-hIL-2 immobilized on the biotinylated mucosal surface of the bladder wall.The mice were monitored for tumor growth and survival.On day 60 after MB49 implantation,the SA-hIL-2-cured mice,which were found to have no hematuria or palpable tumors,were challenged with wild-type MB49 cells implanted into the pretreated bladder and monitored for survival.Results:SA-hIL-2 could be immobilized efficiently and durably on the bladder mucosal surface as long as 7 days.On day 60 after MB49 implantation,9 out of 20 SA-hIL-2-treated mice survived,but all mice in PBS control group died.More importantly,5 out of 9 tumor-free mice in the SA-hIL-2 group were protected against a second intravesical wild-type MB49 tumor challenge.Conclusions:SA-hIL-2 fusion protein could significantly inhibit tumor growth and extend the survival time in the orthotopic model of MB49 bladder cancer.Background and Objective： Intravesical administration of Bacillus Calmette-Gubrin （BCG） after transurethral resection is by far the most effective local therapy for superficial bladder cancer, the fifth most common cancer in the world. However, approximately one-third of patients fail to respond and most patients eventually relapse. In addition, there are pronounced side effects of BCG therapy, such as BCG sepsis and a high frequency of BCG-induced cystitis. This study established a novel immunotherapy through immobilization of streptavidin-tagged human IL-2 （SA-hlL-2） on the biotinylated mucosal surface of bladder wall. Methods： A mouse orthotopic model of MB49 bladder cancer was established by perfusing MB49 cells into mouse bladders. The SA-hlL-2 fusion protein was immobilized on the biotinylated mucosal surface of the bladder wall. Treatment began on day 1 after MB49 implantation, once every 3 days for 6 times. Immunohistochemical assay was performed to assess the persistence of SA-hlL-2 immobilized on the biotinylated mucosal surface of the bladder wall. The mice were monitored for tumor growth and survival. On day 60 after MB49 implantation, the SA-hlL-2-cured mice, which were found to have no hematuria or palpable tumors, were challenged with wild-type MB49 cells implanted into the pretreated bladder and monitored for survival. Results： SA-hlL-2 could be immobilized efficiently and durably on the bladder mucosal surface as long as 7 days. On day 60 after MB49 implantation, 9 out of 20 SA-hlL-2-treated mice survived, but all mice in PBS control group died. More importantly, 5 out of 9 tumor-free mice in the SA-hlL-2 group were protected against a second intravesical wild-type MB49 tumor challenge. Conclusions： SA-hlL-2 fusion protein could significantly inhibit tumor growth and extend the survival time in the orthotopic model of MB49 bladder cancer.

关 键 词：膀胱炎 尿道切除 卡介苗 膀胱癌 

分 类 号：R737.14[医药卫生—肿瘤]