Bladder cancer is the costliest cancer to treat because about 70% of patients with superficial disease will develop tumor recurrence, thus requiring long-term follow-up and repeat interventions. Bacillus Calmette–Guerin (BCG) immunotherapy is the current standard of care for urothelial carcinoma in situ (CIS) and superficial bladder tumors. However, this method suffers from a number of limitations such as BCG intolerance, nosocomial urinary tract infections, and although rare, major systemic BCG reactions. The mechanism of BCG immunotherapy is not fully understood but it is believed to involve an immune response as well as a tumor response. Recently, Lactobacillus species have been shown to induce tumor regression in animal models. Lactobacillus species are generally regarded as safe and may have potential to replace BCG for immunotherapy of bladder cancer. Our work focuses on the development and evaluation of alginate-thiol microspheres with encapsulated Lactobacillus rhamnosus GG (LGG) for potential immunotherapy of bladder cancer. The thiol groups in the microspheres enhance their attachment to bladder luminal surfaces, and as the encapsulated LGG are gradually released from the microspheres, it is expected that the effect of LGG would be prolonged compared with intravesical instillation of free LGG in suspension. It has been earlier postulated that some proteins released by the interaction of these bacterial cells and cancer cells can cause the death of cancer cells. In our work, the concentration and viability of LGG in the microspheres, the LGG release profile and their cytotoxicity on bladder cancer cells were evaluated. In vitro assays showed that when LGG-encapsulated microspheres were placed on the permeable support (0.4 μm pore size) in transwells with cancer cells cultured at the bottom of the wells, ~80% of the cancer cells died after 72 h. Since there is no direct contact between the bacterial and cancer cells, this experiment confirms that the cytotoxic effects of LGG on bladder cancer cells are transmitted through the medium.

Alginate microspheres with encapsulated lactibacillus for potential bladder cancer therapy

249th National Meeting (2015)

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