Alteration of the immune response during cancer development and prevention by administration of a mycobacterial antigen.
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.
Maes
H
H
Microbiology and Genetics Unit, Medical School, Brussels, Belgium.
Taper
H
H
Cocito
C
C
D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000008:administration & dosage*; D006084:Graft Rejection; D006968:Hypersensitivity, Delayed / Q000276:immunology; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000912:Antibodies, Neoplasm; D000942:Antigens, Bacterial; C055539:mycobacterial A60 antigen