Abstract
BackgroundSince 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-α and IL-10 expression and to evaluate antitumour activity.MethodsFor 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-α in the BCG-treated group, as well as increases in TNF-α and IL-10 mRNA in the rBCG-S1PT group.ConclusionThese 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-α and IL-10 cytokine productions may have therapeutic value.
Highlights
Since successful treatment of superficial bladder cancer with Bacillus Calmette Guerin vaccine (BCG) requires proper induction of Th1 immunity, we have developed a recombinant BCG (rBCG)-S1PT strain that induced a stronger cellular immune response than BCG
Following transurethral resection (TUR), BCG is considered an important coadjuvant in the treatment of superficial bladder cancer
The multiple comparisons test (Dunnett) showed significant differences between the groups treated with PBS and BCG (p = 0.007), PBS and rBCG-S1PT (p < 0.001) and BCG and rBCG-S1PT (p < 0.001) (Fig. 1)
Summary
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-α and IL-10 expression and to evaluate antitumour activity. In 1959, initial findings were reported of increased resistance to cancer induced by BCG [1]. Herr described BCG treatment as the most successful immunotherapy used for human tumors [3]. Intravesical BCG is well established in the management of high grade Ta/T1 urothelial carcinoma, as well as CIS [5]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have