The therapeutic effects of R8-liposome-BCG-CWS on BBN-induced rat urinary bladder carcinoma

Anticancer Res. 2011 Jun;31(6):2065-71.

Abstract

Background: The present gold standard for bladder cancer is Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunotherapy, but serious side-effects are common. We previously reported that C3H/HeN mice vaccinated with a mixture of MBT-2 cells and artificial BCG, octaarginine-modified liposomes incorporating the cell wall of BCG (R8-liposome-BCG-CW), significantly inhibited growth of R8-liposome-BCG-CW pretreated MBT-2 cells. Our aim was to determine if a non-live bacterial agent could be as efficacious as live BCG in a model of bladder cancer. We investigated the suppressive effect of liposome-incorporating cell wall skeleton (BCG-CWS) on N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced urinary bladder carcinogenesis in rats.

Materials and methods: F344 rats were fed with BBN and sodium ascorbate for 8 weeks, after which all rats were confirmed to have excreted atypical epithelial cells in the urine. Rats were administered BCG-CW(1.0 mg/rat) or R8-liposome-BCG-CWS (0.1 or 1.0 mg/rat) intravesically once/week for 8 weeks from week 28 to 35 of the experimental protocol.

Results: Rats receiving R8-liposome-BCG-CWS intravesically showed significantly inhibited numbers of tumors, especially those of simple hyperplasia, in comparison with the control rats.

Conclusion: R8-liposome-BCG-CWS administration had inhibitory effects on rat bladder carcinogenesis. These results may indicate a novel adoptive immunotherapy against bladder cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / chemistry
  • Butylhydroxybutylnitrosamine
  • Cell Growth Processes / drug effects
  • Cell Wall / chemistry
  • Immunotherapy / methods
  • Interferon-gamma / immunology
  • Liposomes / administration & dosage
  • Liposomes / chemistry
  • Male
  • Mycobacterium bovis / chemistry
  • Rats
  • Rats, Inbred F344
  • Urinary Bladder Neoplasms / chemically induced
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • BCG Vaccine
  • Liposomes
  • Butylhydroxybutylnitrosamine
  • Interferon-gamma