Bacillus Calmette-Guerin immunotherapy for urothelial carcinoma of the bladder

Abstract

Mycobacterium bovis bacille Calmette-Guerin (BCG) is one of the great success stories of immunotherapy as a treatment for superficial urothelial carcinoma of the bladder. Despite clinical effectiveness in over 50% of patients, the high incidence of local side effects and presence of nonresponders has led to efforts to improve the therapy. Recent advances have suggested a role for neutrophils and TNF-related apoptosis-inducing ligand (TRAIL) in the antitumor inflammatory response. Cell wall components of mycobacteria alone, lowered doses of BCG, and combination with cytokines have been studied as ways to improve the immune response associated with BCG and/or reduce toxicity. This review will discuss the clinical use of BCG, its proposed mechanism of action, and directions of future research to improve efficacy and decrease side effects.

Keywords: BCG; Guerin; TRAIL; bacillus Calmette; bladder cancer; neutrophil; urothelial carcinoma.

Figure 1. Postulated mechanism of action of bacillus Calmette–Guerin

(A) BCG infection of urothelial cells leads to the release of cytokines, such as IL-8. (B) Neutrophils compose the early responding cells to BCG; BCG stimulates release of TRAIL in addition to chemotactic factors. (C) Inflammatory effector cells, such as T cells and macrophages, respond to the neutrophil-secreted chemotactic signals. (D) Cytotoxic cells and TRAIL lead to tumor apoptosis. BCG: Bacille Calmette–Guerin; TRAIL: TNF-related apoptosis-inducing ligand.