EFFECTS OF SEQUENTIAL INTRAVESICAL ADMINISTRATION OF MITOMYCIN-C AND BACILLUS-CALMETTE-GUERIN ON THE IMMUNE-RESPONSE IN THE GUINEA-PIG BLADDER

It has been suggested that intravesical treatment with mitomycin C (MM C) before instillation of bacillus Calmette-Guerin (BCG) improves the antitumor activity of BCG in human bladder cancer. Therefore, we studi ed the immunological effects of sequential intravesical treatment with MMC and BCG in the guinea pig. Four weekly intravesical instillations with MMC preceded six weekly intravesical BCG instillations. The dela yed-type hypersensitivity (DTH) skin reaction evoked by tuberculin pur ified protein derivative (PPD) in guinea pigs receiving BCG intravesic ally appeared slightly earlier in animals pretreated intravesically wi th MMC than in phosphate-buffered saline (PBS)-pretreated animals. How ever, after completing BCG instillations no differences in DTH reactio n were observed between these treatment groups. The extent of the loca l inflammatory reaction in the bladder wall, as well as the parameters measured in the draining iliacal lymph nodes (i.e., the weight, the n umber of leukocytes, and the composition of leukocyte subpopulations), did not differ in animals treated with BCG alone or in combination wi th MMC. A slight increase in the MHC class II expression on the bladde r urothelium was shown if MMC and BCG treatment was combined. The adhe rence of mycobacteria to the bladder wall, measured using H-3-labeled mycobacteria, did not differ between MMC/BCG- and BCG-treated animals. We conclude that MMC does not enhance the immune response against myc obacteria. Therefore, we hypothesize that a possible increased antitum or activity by the combination of MMC and BCG might be due to separate , rather than synergistic, effects of the drugs, namely a cytostatic e ffect of MMC on tumor cells and a local immune response in the bladder evoked by BCG.