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

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.

• Authors: Daher C Chade, Ricardo C Borra, Ivan P Nascimento, Fabiola E Villanova, Luciana C C Leite, Enrico Andrade, Miguel Srougi, Kátia L Ramos, Priscila M Andrade
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 27 Pg. 78 (Nov 28 2008) ISSN: 1756-9966 [Electronic] England
• PMID: 19040745 (Publication Type: Journal Article)

Chemical References

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

Topics

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