It has been shown previously that A60, an antigen complex of Mycobacterium bovis BCG, triggers humoral and cellular immune reactions in vivo and lymphocyte-dependent macrophage activation in vitro. In the present work, the ability of A60 to prevent murine tumour development, in conjunction or not with irradiated isologous cancer cells, was explored with Taper liver tumour (TLT), a mammary-derived neoplasm (EMT6), and Lewis lung carcinoma (3LL). Repeated injections of A60 prior to challenge reduced the incidence of EMT6 and 3LL solid tumours and increased life span. This effect was enhanced by simultaneous administration of gamma-irradiated cancer cells (80-100% suppression of EMT6 and 3LL tumour growth). In mice developing or rejecting tumours, the status of humoral and cellular immunity was evaluated by A60-based immunoassays. Tumor development was accompanied by a rapid decrease of both anti-A60 IgG titre in blood and A60-triggered delayed hypersensitivity reactions. Moreover, A60-induced T lymphocyte proliferation and macrophage-dependent autologous cancer cell cytolysis declined progressively during the course of tumour growth. In case of successful immunotherapy, a pattern similar to that of unchallenged controls was observed. Our results suggest that A60 promotes cancer rejection via tumour infiltration by lymphocytes and macrophages activated by A60-specific T lymphocytes. An increased processing of tumour-specific antigens and activation of tumour-infiltrating lymphocytes is induced by administration of irradiated cancer cells in conjunction with A60.

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The antigen complex A60 of Mycobacterium bovis bacillus Calmette-Guérin protected mice against experimental tuberculous infection, and prevented cancer development after challenge with EMT 6 cells. Although humoral and cellular immune reactions elicited by A60 in vivo remained unaffected in cases of tumor rejection, they were suppressed in the case of neoplastic growth. In the present work, these in vivo observations were analyzed by in vitro techniques. Activated macrophages played a major role, and cytolytic T lymphocytes a minor role, in A60-promoted cancer cell cytolysis leading to tumor rejection. In vitro, EMT 6 cells weakly inhibited the proliferation of A60-specific B lymphocytes and strongly inhibited the functions of activated macrophages. However, the collapse of both humoral and cellular immune reactions during the course of cancer development was also accompanied by an inhibitory action of EMT 6 cells on the multiplication and functions of A60-specific T lymphocytes. Tumor-dependent repression of macrophage activation was therefore due to both a direct action of tumor cells on macrophages and an indirect one via inhibition of macrophage-activating T cell functions. On the other hand, tumor-induced collapse of the anti-A60 Ig synthesis was mainly due to inhibition of B-cell-activating T cells, with a weaker direct effect of tumor cells on B lymphocytes. Consequently, A60 and tumor cells exert opposite effects on the immune system at several levels.