Injection of living Mycobacterium bovis (strain BCG) into established intradermal tumors caused tumor regression and prevented the development of metastases.

The intradermal inoculation of mixtures containing living tumor cells and living Mycobacterium bovis (strain BCG) into unimmunized syngeneic guinea pigs results in an inflammatory reaction to the BCG, and there is no progressive tumor growth. In the absence of BCG the tumor grows progressively, metastasizes, and kills the animal. By conventional methods, it has not been possible to immunize syngeneic guinea pigs to the tumor used. Guinea pigs that receive mixtures of BCG and tumor cells, however, develop specific systemic tumor immunity as measured by delayed cutaneous hypersensitivity and by suppression of tumor growth.

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SUMMARY : Effects of mixing living BCG with living tumor cells on the growth of the tumor cells in the intradermally inoculated mice and induction of the tumor immunity were investigated with various syngeneic and allogeneic mouse tumor systems. Tumor immunity was assessed from transplant resistance against challenge tumor grafts, macrophage migration inhibition and peritoneal macrophage disappearance.The effects of BCG-tumor cell mixtures varied depending upon the tumor lines and also upon the experimental conditions employed. From the modes of the effect, the tumors used were classified into the following three types : (1) rejecting the primary tumor grafts and inducing the tumor-specific, cell-mediated immunity; (2) rejecting the primary tumor grafts but inducing no detectable tumor immunity; and (3) not rejecting the primary tumor grafts even in BCG-sensitized mice. These types seemed to correlate with the levels of antigenicity and the growth rates of the tumor cells. Number of the tumor cells in the inoculum, in addition to the tumor lines, largely influenced the effects. For the optimal suppression of the growth of tumor cells in the primary inocula, generally required were the following factors : (1) prior sensitization of mice to BCG, (2) direct contact between BCG and tumor cells, and (3) intradermal route of injection.

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