Bacillus Calmette–Guérin strain differences as the basis for immunotherapies against bladder cancer

: In the past 40 years, intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guerin has been carried out as the most effective treatment for preventing local recurrences and tumor progression of non-muscle-invasive bladder cancer. Bacillus Calmette-Guerin is a family of vaccines derived in 1921 by the in vitro attenuation of Mycobacterium bovis. Subsequently, bacillus Calmette-Guerin seed lots were spread around the world, and both phenotypic and genotypic differences among the strains have been compiled. In recent genomic comparisons, the evolution of the different bacillus Calmette-Guerin substrains has begun to emerge. However, some of these genetic alterations in bacillus Calmette-Guerin strains have yet to be shown to affect the therapeutic effects and/or adverse effects. There are thus ongoing research efforts to assess the effects of these genetic alterations on the properties of bacillus Calmette-Guerin strains, with the ultimate goal of identifying an ideal bacillus Calmette-Guerin strain for treatment of non-muscle-invasive bladder cancer and providing clues for the improvement of bacillus Calmette-Guerin strains. The present review provides a history of bacillus Calmette-Guerin immunotherapy, and discusses the genetic differences among bacillus Calmette-Guerin strains, the different clinical outcomes afforded by bacillus Calmette-Guerin strains and possible future developments.