Immunological prevention of a multigene cancer syndrome.
Vaccines effectively prevent the onset of tumors in transgenic mice carrying activated oncogenes; however, human tumors are caused by combined alterations in oncogenes and oncosuppressor genes. We evaluated the impact of prophylactic vaccines in HER-2/neu transgenic, p53 wild-type/null mice that succumb to an aggressive cancer syndrome comprising mammary and salivary gland carcinomas and rhabdomyosarcoma. A vaccine made of allogeneic mammary carcinoma cells expressing HER-2/neu and interleukin 12 afforded long-term protection from tumor onset. Tumor prevention was mediated by T cell-derived cytokines, in particular gamma-interferon, and by anti-HER-2/neu antibodies. HER-2/neu expression was inhibited in target tissues of vaccinated mice, and somatic loss of the wild-type p53 allele did not occur. A highly effective vaccine against a single oncoprotein induced a powerful immune response that arrested multistep carcinogenesis in distinct target tissues.
Croci
Stefania
S
Cancer Research Section, Department of Experimental Pathology, University of Bologna, Bologna, Italy.
Nicoletti
Giordano
G
Landuzzi
Lorena
L
De Giovanni
Carla
C
Astolfi
Annalisa
A
Marini
Chiara
C
Di Carlo
Emma
E
Musiani
Piero
P
Forni
Guido
G
Nanni
Patrizia
P
Lollini
Pier-Luigi
PL
D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D018734:Genes, erbB-2; D016158:Genes, p53; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics / Q000517:prevention & control*; D051381:Rats