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.
Institute of Biotherapy, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, PR China.
Xin
X
Huang
Hong-sheng
HS
Yu
Zhong
Z
Chen
Jin-Long
JL
Li
Zhi-Ming
ZM
Hu
Ji-Min
JM
Gao
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