Reduction of bladder tumor growth in mice treated with intravesical Bacillus Calmette-Guérin and its correlation with Bacillus Calmette-Guérin viability and natural killer cell activity.

The effect of intravesical Bacillus Calmette-Guérin (BCG; Pasteur strain) treatment on the frequency of implantation and growth rate of the murine transitional cell carcinoma of the bladder, MBT-2, was studied. MBT-2 cells were instilled into the bladder immediately after electrocauterization, and BCG instillations (40, 80, and 160 micrograms/instillation) were initiated 24 hr later and continued on a weekly basis for 4 weeks. BCG treatment significantly (p less than 0.0002) reduced the incidence of tumor implantation in a dose-dependent manner and resulted in significantly (p less than 0.0001) smaller tumors when they appeared in BCG-treated mice. The therapeutic effect of BCG correlated with augmentation of natural killer cell (NK) activity and positive purified protein derivative (PPD) footpad reactions. In experiments in which treatment was initiated with rapidly growing BCG organisms (10(7) colony-forming units/mg), tumor implantation was inhibited, there was a dose-dependent increase in NK activity, and mice had positive footpad reactions in PPD. In experiments in which BCG with reduced viability (10(6) colony-forming units/mg) and slower growth rates was used for treatment, no significant inhibition of tumor implantation was observed, NK activity was depressed, and PPD footpad tests were uniformly negative. The results suggest that the therapeutic effects of BCG therapy in this murine model correlate with augmentation of NK activity and positive footpad reactions to PPD and further suggest that the viability and growth rate of BCG organisms are important factors in determining the efficacy of intravesical BCG therapy.