Immunomodulatory effects of recombinant BCG expressing pertussis toxin on TNF-alpha and IL-10 in a bladder cancer model
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 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-alpha and IL-10 cytokine responses were measured by qPCR. Experiment II was performed the same 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.
Conclusions: 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 production may have therapeutic value.
Author: Daher C Chade, Ricardo C Borra, Ivan P Nascimento, Fabiola E Villanova, Luciana CC Leite, Enrico FM Andrade, Katia Ramos, Miguel Srougi and Priscila M Andrade
Credits/Source: Journal of Experimental &Clinical Cancer Research 2008, 27:78
Published on: 2008-11-28
Copyright by the authors listed above - made available via BioMedCentral (Open Access). Please
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