Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model

J Exp Clin Cancer Res. 2008 Nov 28;27(1):78. doi: 10.1186/1756-9966-27-78.

Abstract

Background: Since successful treatment of superficial bladder cancer with BCG requires proper induction of Th1 immunity, we have developed a rBCG-S1PT strain that induced a stronger cellular immune response than BCG. This preclinical study was designed to compare the modulatory effects of BCG and rBCG-S1PT on bladder TNF-alpha and IL-10 expression and to evaluate antitumour activity.

Methods: For Experiment I, the MB49 bladder cancer cell line was used in C57BL/6 mice. Chemical cauterization of the bladder was performed to promote intravesical tumor implantation. Mice were treated by intravesical instillation with BCG, rBCG-S1PT or PBS once a week for four weeks. After 35 days the bladders were removed and weighed. TNF- and IL-10 cytokine responses were measured by qPCR. Experiment II was performed in the same manner as Experiment I, except the animals were not challenged with MB49 tumor cells.

Results: rBCG-S1PT immunotherapy resulted in bladder weight reduction, compared to the BCG and control group. There were increases in TNF-alpha in the BCG-treated group, as well as increases in TNF-alpha and IL-10 mRNA in the rBCG-S1PT group.

Conclusion: These data indicate a significant reduction of bladder tumor volume for the rBCG group, compared to the BCG and PBS groups. This suggests that rBCG could be a useful substitute for wild-type BCG and that the potential modulation between TNF-alpha and IL-10 cytokine productions may have therapeutic value.

MeSH terms

  • Animals
  • BCG Vaccine / genetics
  • BCG Vaccine / immunology
  • BCG Vaccine / pharmacology*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cancer Vaccines / pharmacology*
  • Carcinoma, Transitional Cell / immunology
  • Carcinoma, Transitional Cell / therapy*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Immunologic Factors / immunology
  • Immunologic Factors / pharmacology
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium bovis / genetics
  • Mycobacterium bovis / immunology
  • Pertussis Toxin / biosynthesis
  • Pertussis Toxin / genetics
  • Pertussis Toxin / immunology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Random Allocation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology*
  • Urinary Bladder Neoplasms / immunology
  • Urinary Bladder Neoplasms / therapy*

Substances

  • BCG Vaccine
  • Cancer Vaccines
  • Immunologic Factors
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Pertussis Toxin