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

Studies in recent years have shown various effects of bacillus Calmett e Guerin organisms on the human immune system. In the present study, t he direct effects of bacillus Calmette Guerin (BCG) (as used for the c linical management of superficial bladder cancer) on bladder tumour ce lls were investigated. Using a proliferation assay, changes in the gro wth rates of tumour cells were studied following direct exposure to BC G. The effects of variations in the BCG dose, and in the viability of BCG organisms were investigated and our initial observations concernin g the antiproliferative effects of interferon-garnma were extended. Th e main finding of these studies is the direct immuno-modulatory effect s of BCG organisms on the proliferative capacity of human tumour cells . Previously these alterations in the growth rate of bladder cancer ce lls, which are observed following patient therapy, were attributed to the production of various cytokines. However, after exposure to BCG th e growth of tumour cell lines was suppressed in a dose and time depend ent manner. Furthermore, both viable and nonviable bacilli can exert t his action although heat killed BCG may be less effective in doing so. In concordance with our earlier study, interferon-gamma exerted marke d antiproliferative effects against eight tumour cell lines. Furthermo re, a 12 hour pulse of cytokine was sufficient to suppress the growth of tumour cells. This is an important finding as cytokine is not detec ted in patient's urine later than 12 hours after immunotherapy. No con sistent 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 dir ect effects upon tumour cells in vivo and thus ease the load on the im mune responses leading to the eventual eradication of tumour.