Immunoprophylaxis of syngeneic methycholanthrene-induced murine sarcomas with Bacillus Calmette-Gu\ue9rin and tumor cells

We studied the conditions necessary for living Mycobacterium bovis strain Bacillus Calmette-Gu\ue9rin (BCG) to augment the capacity of tumor cells to induce specific rejection immunity in healthy mice against transplants of chemically induced fibrosarcomas. Immunization by implantation of tumor cells alone and excision of the resulting growth was compared to that induced by implantation of tumor cells in admixture with BCG followed by excision of the injection site. The numbers of tumor cells and BCG organisms used for immunization were varied to determine the quantities and proportions of those materials required for greatest augmentation of the ability of the animals to reject a challenge of live tumor cells. To assess the degree of host resistance produced by immunization, mice were challenged by i.d. injection of graded doses of living tumor cells. As the number of tumor cells in immunizing mixtures was decreased, an amount was found below which no dose of BCG augmented the capacity of the tumor cells to induce specific host resistance. As the dose of BCG in immunizing mixtures was decreased, an amount was found below which no dose of tumor cells was more effective than tumor cells alone. With each of the fibrosarcomas studied, immunization with optimal quantities of BCG and tumor cells was more effective in producing tumor rejection immunity than were tumor cells alone. Immunization with BCG alone did not increase the ability of the animals to reject tumor. When the specificity of immunity produced by immunization with tumor and BCG was analyzed, two of three fibrosarcomas were found to be cross-protective. Animals immunized with normal murine, syngeneic adult or embryonic tissue, or neoplastic mammary tissue, each in admixture with BCG, were not protected against the growth of the murine fibrosarcoma transplants. The murine fibrosarcomas that were capable of inducing cross-protection released ecotropic murine leukemia virus(es) and contained lactic dehydrogenase virus. The ability of fibrosarcomas to induce cross-protection persisted after tumors were rendered free of lactic dehydrogenase virus by passage in vitro in tissue culture flasks. Resistance to tumor growth was achieved in mice that were challenged 2 to 3 weeks after injection of vaccine. Mice challenged on the same day as the injection of vaccine were not significantly protected against growth of the tumor cells in the challenge inoculum