Superantigen enhanced protection against a weak tumor-specific melanoma antigen: implications for prophylactic vaccination against cancer.
B16F10 melanoma is a tumor derived from C57BL/6 mice that has been found to be poorly immunogenic and highly aggressive. Here we have shown that vaccination of mice with irradiated B16F10 cells followed by treatment with a combination of staphylococcal enterotoxins A and B (SEA/SEB) leads to significant and specific protection against subsequent challenge with viable B16F10 cells (at least 25-fold greater than a lethal dose). Also, 75% of mice surviving over 150 days remained tumor-free after rechallenge with viable B16F10 cells, evidence of the development of strong immunologic memory. Additional studies showed increases in CD4(+) and CD8(+) T-cell populations, cytotoxic T-lymphocyte activity and interferon-gamma production, all of which may contribute to enhanced survival. Furthermore, failure to produce protection in either CD4(-/-) or CD8(-/-) T-cell knockout mice is evidence that CD4(+) and CD8(+) T cells play an essential role in induction of immunity. These results show that superantigen administration subsequent to vaccination with inactivated tumor cells results in protective antitumor immunity. Thus, prophylactic vaccination against cancer is a feasible method for arming the immune system prior to the incidence of cancer.
Kominsky
S L
SL
Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Torres
B A
BA
Hobeika
A C
AC
Lake
F A
FA
Johnson
H M
HM
D000818:Animals; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000276:immunology*; D058950:Melanoma-Specific Antigens; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000276:immunology*; D018089:Superantigens / Q000494:pharmacology*; D014611:Vaccination
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D004768:Enterotoxins; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma