Drug Discov Ther. 2008;2(3):168-177.

Injection of cell-wall skeleton of Mycobacterium bovis BCG draining to a sentinel lymph node eliminates both lymph node metastases and the primary transplanted tumor.

Kashiwazaki Y, Murata M, Sato T, Miyauchi M, Nakagawa M, Fukushima A, Chiba N, Azuma I, Yamaoka T

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.

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