Based on recent developments in innate immunity, we focused on a microbial immunostimulator for
cancer immunotherapy. If innate immunity is properly activated,
tumor antigens distributed endogenously in
cancer patients will be exploited to activate
tumor immunity. We chose the
cell-wall skeleton of M. bovis BCG (BCGCWS) and investigated the potential of monotherapy without exogenous
tumor antigens. We used strain 2 guinea pigs bearing syngenic line 10
hepatoma, which is an excellent disease model of spontaneous
lymph node metastasis, and examined the
tumor-eradicating activity of highly purified BCG-CWS (SMP-105), excluding the effect of local
inflammation on
tumor growth. SMP-105 eliminated both established
metastases and the implanted
tumor, when injected into different but not distant sites from the
tumor, whereas, when injected into the opposite side, neither
metastases nor the primary
tumor was eradicated. SMP-105 was observed in the draining lymph node engulfed by phagocytes, presumably macrophages or dendritic cells, but was not detected in distant lymph nodes or the spleen. It took about 2 weeks until the
tumor-eliminating effect was observed. Taken together it is considered that macrophages or dendritic cells were activated by SMP-105 and encountered
tumor cells in the sentinel lymph node to generate
tumor immunity during the lag time. In conclusion, we suggested the potential of mono-
therapy with a strong immunostimulator and that SMP-105 is a most promising agent for
cancer immunotherapy. Separate injection from
tumor draining to a sentinel lymph node using classical guinea pig models will be a useful method for investigating immunostimulators.