Ratha Mahendran
National University of Singapore
Singapore
Title: Bladder cancer immunotherapy with Lactobacillus rhamnosus strain GG
Biography
Biography: Ratha Mahendran
Abstract
Bladder cancer is characterized by frequent recurrences which may progress to muscle invasive disease. Current immunotherapy with Mycobacterium bovis, Bacillus Calmette-Géurin (BCG) has serious side-effects and some subjects do not respond. This failure to respond has been attributed to an inability to mount an effective immune response. In a murine model of bladder cancer intra-vesical Lactobacillus rhamnosus strain GG (LGG) instillations were as effective as BCG. Dose and time dependant effects of LGG on immune activation were analyzed using murine bone marrow derived DC or neutrophils stimulated with LGG at ratios of 5:1, 10:1 and 100:1 (LGG: Cells). DC maturation and cytokine production was examined after 2 hours and 18 hours co-culture and their ability to activate T cells were also determined. A 2 hours exposure to a 100:1 or an18 hours to a 5:1 or 10:1 ratio of LGG: Cells induced the highest production of IL-12 and up regulation of CD40, CD80, CD86 and MHC II on DC. T cell production of IFN-g and IL-2 was significantly greater when stimulated with DC activated with 10:1 LGG to cells, either directly or indirectly via neutrophils. DC or DC activated by neutrophils exposed to a low dose of LGG generally induce greater Th1 polarization in T cells compared to a high LGG dose and could potentially exert stronger anti-tumor effects.