Analysis of anti-bladder tumor with BCB derivative producing fusion protein between Ag85B and IL-2 or IL-18

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Two immunological methods such as LAK(IL-2LAK) and TIL are used for the treatment of cancer. In LAK, NK and T cells, especially, cytotoxic T lymphocyte (CTL), are activated by autocrine or paracrine pathway through IL-2/IL-2R and kill cancer cells. In this experiment, we already reported that when mice were intra-nasally immunized with inactivated BCG plus mutant LT, the cellular immunity for inactivated BCG was highly induced (Vaccine,24,3591,2006). Moreover, when the spleen cells from mice intra-nasally immunized with inactivated BCG plus mLT or live BCG were prepared and stimulated by inactivated or live BCG, respectively,in vitro, IL-2 was induced higher in the spleen cells from mice immunized with inactivated BCG plus mLT than those with live BCG. These data suggest the possibility that when mice immunized with inactivated BCG plus mLT might induce identical anti-cancer affect as live BCG. Then, we examined whether the immunization of mice with inactivated BCG plus mLT or some cytokine such as IL-2 or IL-18 might induce similar anti-cancer effect, especially for bladder cancer, to live BCG. Moreover, we construct the vector containing Ag85B-IL-2 or Ag85B-IL-2IL-18 fusion gene to determine whether BCG carrying these constructed vector might decrease the growth of bladder tumor.