The characterization and efficacy of BCG mediated tumor activity in guinea pigs with regional and/or systemic malignancy

Transplanted syngeneic line 10 hepatocarcinomas established in the skin of inbred guinea pigs (strain 2) regress and regional lymph node metastases are eliminated after intratumoral injection of viable Mycobacterium bovis strain BCG. During the course of this reaction there is the development of systemic tumor immunity. Macrophages from BCG tumor cured guinea pigs at effector to target cell ratios of 10:0 and 100:1 are cytotoxic in vitro to line 10 tumor cells, and this cytotoxicity was potentiated by autologous serum. The approach to evaluate the efficacy of BCG induced systemic tumor immunity in vitro, for regional as well as systemic tumor, was to develop a competition assay using increasing doses of intravascular disseminated line 10 tumor cells in animals with established regional tumors. The efficacy of intratumoral BCG injection in producing regression of regional tumor is abrogated by initial intravascular doses of 10³ to 10⁶ line 10 cells. That the vascular systemic tumor burden diminished the effective systemic tumor immunity was demonstrated by the inability of animals with systemic tumor burdens to reject contralateral challenge of line 10 tumor cells. Survival studies clearly demonstrate that a significant therapeutic effect could be achieved in guinea pigs with combined immunotherapy and surgery.