Immunotherapeutic effectiveness of BCG inactivated by various modalities

Factors responsible for the limited effectiveness of Bacillus Calmette-Guérin (BCG) immunotherapy are completely understood. One limitation is that although the effect is dose-related, high-dose administration increases the risk of BCG toxicity, possibly the result of disseminated BCG infection. In the present study, we compared the relative effectiveness of Tice lyophilized BCG which was inactivated by heat, sonication, irradiation, streptomycin, or isoniazid (INH). The model systems were the 13762A rat mammary adenocarcinoma and the line 10 guinea pig hepatoma. In the 13762A system, tumor were injected on day 7 with living or killed BCG preparations, or with Corynebacterium parvum as a positive control. Tumors were excised on day 20. Rats treated with surgery alone usually died within 40--50 days with extensive metastases to lymph nodes, lungs, and viscera. Guinea pig line 10 hepatoma was treated with vaccine containing irradiated tumor cells and BCG. In both the rat and guinea pig models, BCG inactivated by means of irradiation was effective as viable BCG and heat-killed BCG also had a strong effect. Streptomycin treatment diminished the efficacy of the BCG and sonication destroyed BCG effectiveness even though the organisms were not all killed. The INH treatment of tumor-bearing rats did not alter the benefits of single or repeated injections of high-dose viable BCG, irradiated BCG, or C parvum. We conclude that inacativation of BCG with heat, irradiation, or INH host treatment preserves but does not improve the immunotherapeutic benefits of BCG.