Harnessing the Host Immune Response to Infection – BCG Immunotherapy for Bladder Cancer.
Résumé
Bacillus Calmette–Guérin, or BCG, an avirulent strain of Mycobacterium bovis, was developed as a vaccine for the prevention of tuberculosis. BCG’s success in disease prevention resulted in the vaccination of billions of individuals. The observation that bacterial components could induce tumor regression, coupled with reports that BCG-vaccinated individuals demonstrated reduced cancer incidence, led to the development of BCG as an immunotherapeutic agent. The pioneering work of Morales and colleagues in the 1970s, demonstrating that direct instillation of live BCG into the bladder of patients with nonmuscle invasive bladder cancer prevented tumor recurrence, laid the path for what is arguably the most successful immunotherapy to date. Notably, although much work has focused on how BCG mediates tumor immunity, important unknowns regarding the mechanism of action remain. Nonspecific innate pathways, such as neutrophil-mediated killing, and adaptive immunity, such as induction of BCG- and tumor-specific T cells, likely work in concert to exert anti-tumor effects. Finally, as the mechanisms of action are unraveled, questions of pharmaco-equivalency of BCG substrains have arisen with respect to the clinical management of bladder cancer patients. Thus, while BCG immunotherapy is currently the standard of care for nonmuscle invasive bladder cancer, there exists great opportunity to improve upon this treatment through additional research and clinical trials.