Immunostimulation in the urinary bladder by local application of Nocardia rubra cell-wall skeletons (Rubratin) and bacillus Calmette-Guerin as therapy for superficial bladder cancer: A comparative study

Twelve patients with superficial bladder cancer were treated with intravesi cal instillations of Rubratin (ASTA Pharma AG, Frankfurt, Germany), a cell- wall preparation of Nocardia rubra. The objective was to compare the immuno stimulating effect of Rubratin with that of bacillus Calmette-Guerin (BCG), Local immunostimulation was determined by cytokine induction in serially c ollected urine samples during the first 24 h after each instillation, leuko cyte influx into the urine, and phenotypic analysis of the lymphocyte fract ion. Levels of Rubratin-induced interleukin (IL)-1 beta, IL-6, and tumor ne crosis factor-a: were significantly elevated compared with pretherapy level s. Rubratin induced leukocyte influx into the urine. T-cell activation (IL- 2 receptor and human leukocyte antigen-DR expression) can be induced, and C D4:CD8 cell ratios can be increased. All parameters indicated that Rubratin -induced immunostimulation was less than that associated with BCG. In concl usion, although local Rubratin-induced immunostimulation occurs in a limite d number of patients, the amount of immunocompetent cells attracted to the bladder seems to be less than that associated with BCG therapy, thus result ing in lower levels of cytokine production (which may reflect less clinical efficacy).