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In a transplantable hepatocarcinoma (L10) model of inbred Sewall Wright strain 2 guinea pigs, established micrometastatic tumor foci could be eliminated from the viscera by specific tumor immunity induced by the systemic effect of a BCG-L10 tumor cell vaccine. The conditions of vaccine preparation and regimen were rigid, and a dose dependency for both BCG and tumor cells existed. Comparison of the influence of cryobiologic preservation procedures on the tumor cells to be used in the vaccine showed that cells frozen by an optimized cryobiologic procedure, improved for maintenance of viable cells, were more effective than cells frozen by a conventional glycerol method. The glycerol method resulted in a lower percentage of viable cells, and the effectiveness of the vaccine was greatly diminished. Thus some past failures of active specific immunotherapy could be associated with acute antigenic exposures resulting from suboptimal cryobiologic preservation of tumor cells in the vaccine preparation instead of prolonged or chronic tumor cell antigenic exposure resulting from optimal cryobiologic procedures.

In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor.