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.
