BACILLUS-CALMETTE-GUERIN (BCG) ORGANISMS DIRECTLY ALTER THE GROWTH OF BLADDER-TUMOR CELLS

Studies in recent years have shown various effects of bacillus Calmette Guerin organisms on the human immune system. In the present study, the direct effects of bacillus Calmette Guerin (BCG) (as used for the clinical management of superficial bladder cancer) on bladder tumour cells were investigated. Using a proliferation assay, changes in the growth rates of tumour cells were studied following direct exposure to BCG. The effects of variations in the BCG dose, and in the viability of BCG organisms were investigated and our initial observations concerning the antiproliferative effects of interferon-garnma were extended. The main finding of these studies is the direct immuno-modulatory effects of BCG organisms on the proliferative capacity of human tumour cells. Previously these alterations in the growth rate of bladder cancer cells, which are observed following patient therapy, were attributed to the production of various cytokines. However, after exposure to BCG the growth of tumour cell lines was suppressed in a dose and time dependent manner. Furthermore, both viable and nonviable bacilli can exert this action although heat killed BCG may be less effective in doing so. In concordance with our earlier study, interferon-gamma exerted marked antiproliferative effects against eight tumour cell lines. Furthermore, a 12 hour pulse of cytokine was sufficient to suppress the growth of tumour cells. This is an important finding as cytokine is not detected in patient's urine later than 12 hours after immunotherapy. No consistent pattern of growth altering effect was observed with any of the other cytokines tested (IL-1-alpha, IL-2, IL-3, IL-4, IL-6, IL-7, IL-8, GM-CSF). Our study suggests that BCG organisms per se may exert direct effects upon tumour cells in vivo and thus ease the load on the immune responses leading to the eventual eradication of tumour.