Research ArticleBladder Cancer

Preexisting BCG-Specific T Cells Improve Intravesical Immunotherapy for Bladder Cancer

Science Translational Medicine  06 Jun 2012:
Vol. 4, Issue 137, pp. 137ra72
DOI: 10.1126/scitranslmed.3003586

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Bugs as Drugs

Although still in its infancy for the treatment of many tumor types, immunotherapy has been and remains the standard of care for patients with bladder cancer. The concept behind this success is repeated instillations of bacillus Calmette-Guérin (BCG; the same bacteria used as a vaccine for Mycobacterium tuberculosis) in the bladder, inducing an immune response that fights the cancer. The clinical response rate in bladder cancer patients is 50 to 70%, higher than any other immunotherapy but still leaving room for improvement. Biot et al. provide new insight into the mechanisms behind BCG’s success in the bladder and suggest that parenteral BCG exposure may boost the success rate for bladder cancer treatment.

Using a mouse model of bladder cancer, the authors show that a single instillation of BCG induced an immune response, but repetitive instillations were required for robust T cell trafficking to the bladder. Previous parenteral exposure to BCG overcame this requirement in the mice, inducing an enhanced innate immune response, accelerating T cell trafficking to the bladder, and improving the immune response to the tumor. Furthermore, bladder cancer patients who had preexisting immunity to BCG (secondary to their childhood M. tuberculosis vaccination) showed improved recurrence-free survival after standard BCG therapy relative to those patients without preexisting immunity. Thus, immunizing BCG-naïve cancer patients before therapy may provide a simple strategy that could improve therapeutic response.