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.
OBJECTIVE
Intravesical administration of Bacillus Calmette-Guerin (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.
Huang
Xin
X
Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
Yu
Hong-sheng
HS
Chen
Zhong
Z
Li
Jin-Long
JL
Hu
Zhi-Ming
ZM
Gao
Ji-Min
JM
D000818:Animals; D019921:Biotinylation; D045744:Cell Line, Tumor; D005260:Female; D055767:Immobilized Proteins / Q000378:metabolism / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D007376:Interleukin-2 / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000378:metabolism; D009368:Neoplasm Transplantation; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000627:therapeutic use*; D019809:Streptavidin / Q000378:metabolism / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000276:immunology / Q000628:therapy*
C508594:IL2 protein, human; D055767:Immobilized Proteins; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D019809:Streptavidin