Long Term Protection in Bladder Cancer Following Intralesional Immunotherapy

Abstract

Despite effective treatment of existing tumors, patients with bladder cancer remain at risk of developing new tumors. Effective immunotherapy may lower that risk. To test this hypothesis, mice that had survived transitional cell carcinoma (MBT2) transplantation with the aid of bacillus Calmette-Guerin immunotherapy were randomized and tested for long term protective immunity against bladder carcinoma. Fifty-one tumor-free mice that had survived tumor challenge 10 to 15 months previously were randomized into 3 groups to receive intradermal tumor inoculation and intraperitoneal levamisole, intralesional Tice strain bacillus Calmette-Guerin, or intralesional saline. Fifteen previously unchallenged animals also received tumor and intralesional saline. All 3 groups of survivors had less tumor growth (p <0.01) than nonsurvivor controls. Even among survivors, additional bacillus Calmette-Guerin immunization, but not levamisole treatment, significantly inhibited tumor growth (p <0.01). A 2nd experiment compared 22 nonimmune mice, 21 mice preimmunized intravenously with 300 μg. of bacillus Calmette-Guerin cell walls, and 18 mice that had survived MBT2 by 8 months after live bacillus Calmette-Guerin treatment. Nonimmune and survivor groups were randomly subdivided into saline or treatment groups. Cell wall-preimmunized mice were divided into matching groups according to footpad response to purified protein derivative. The cell-wall preimmunized and nonimmune mice received the immunostimulant P3+Re-glycolipid or the carrier solution alone. The group of survivors received either intralesional saline or live bacillus Calmette-Guerin. Both bacillus Calmette-Guerin and saline-treated groups had significantly less tumor growth (p <0.001) than nonsurvivor controls. Animals treated with P3-Re-glycolipid (with or without preimmunization with cell wall) did not differ from nonsurvivor control. Footpad response to purified protein derivative did not correlate with tumor growth in these mice. Our results suggest that intralesional bacillus Calmette-Guerin immunotherapy can afford long term protection from transplanted bladder cancer, and that live bacillus Calmette-Guerin is superior to levamisole and P3 + Re-glycolipid + bacillus Calmette - Guerin cell walls in the treatment of bladder cancer.