RESEARCH of the intravesical immunotherapy for human bladder cancer

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671796
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Urology
• Research Institution: University of Tokyo
• Principal Investigator: KAMEYAMA Shuji University of Tokyo Hospital Internal-Medicine, 医学部・附属病院, 講師 (90186015)
• Co-Investigator(Kenkyū-buntansha): TOMETA Kyoichi University of Tokyo Hospital Lecturer Assistant Professor, 医学部・附属病院, 助手 (20272578)
• Project Period (FY): 1996 – 1997
• Keywords: human bladder cancer / animal model / intravesical BCG instillation / cytokine

Research Abstract

Intravesical instillation of live BCG is a most effective therapy against superficial bladder carcinomas. BCG in clinical use is a live bacteria, having serious local and systemic side effects. Several cytokines are known to be secreted into the urine after intravesical BCG instillation. We tested cytokine inductions and antitumor effect in vivo by killed BCG using animal models. We have developed a new in vivo model for studying intravesical immunotherapy. The model consists of a heterotopically transplanted bladder (HTB) in the retroperitoneal space of a C3H/He N mouse and connected with a subcutaneous reservoir. We used autoclaved BCG (connaught strain) as a killed one. Forty-eight hours after instillation of BCG (0.4mg/0.2ml PBS), supernatants of aspirates in HTBs were collected for cytokine assay by ELISA. MBT-2 cancer cells conjugated with 0.5mg of BCG were implanted on the back of C3H/HeN mice. The tumor growth was compared among groups treated with killed BCG, live BCG and PBS. TNFa levels induced in HTBs were as follows ; 356【+!-】146 (M【+!-】SE) in control group (N=6), 3006【+!-】311ィイD1★ィエD1 in live BCG group (N=7), and 3175【+!-】158ィイD1★ィエD1 pg/ml in killed BCG group (ィイD1★ィエD1p<0.01). Tumor growth in vivo was completely suppressed by the treatment with killed BCG as well as live BCG. Autoclaved killed BCG as well as live BCG produced marked induction of cytokines in this animal model. These results show the possibility of BCG modification in intravesical treatments.