Inhibition of murine bladder tumor growth by bacille Calmette-Guerin: Lack of a role of natural killer cells

Abstract

Intravesical instillation of bacille Calmette Guerin (BCG) currently is considered the most effective treatment for recurrent superficial bladder cancer, but little is known about the mechanism of action. We have adapted a model in which the mouse bladder tumor, MBT-2, is implanted directly into the bladder to examine the mechanism by which BCG inhibits tumor growth. The intravesical administration of BCG inhibited MBT-2 implantation in a dose-dependent manner. Concomitantly, natural killer (NK) activity was augmented in a dose-dependent manner. Conversely, BCG doses which did not augment NK activity lacked antitumor activity. Linear regression analysis showed a significant correlation between the antitumor activity of BCG and modulation of NK activity (correlation coefficient, 0.991). Additional studies were performed in which NK activity was abrogated by administration of anti-asialo-GM 1 serum. NK activity was depressed in spleens and lymph nodes of both normal and BCG-treated mice. Abrogation of NK activity did not alter the efficacy of BCG therapy suggesting that NK cells are not a major contributor to the antitumor activity of BCG.