PT  - JOURNAL ARTICLE
AU  - Nanni, Patrizia
AU  - Landuzzi, Lorena
AU  - Nicoletti, Giordano
AU  - De Giovanni, Carla
AU  - Rossi, Ilaria
AU  - Croci, Stefania
AU  - Astolfi, Annalisa
AU  - Iezzi, Manuela
AU  - Di Carlo, Emma
AU  - Musiani, Piero
AU  - Forni, Guido
AU  - Lollini, Pier-Luigi
TI  - Immunoprevention of Mammary Carcinoma in HER-2/<em>neu</em> Transgenic Mice Is IFN-γ and B Cell Dependent
AID  - 10.4049/jimmunol.173.4.2288
DP  - 2004 Aug 15
TA  - The Journal of Immunology
PG  - 2288--2296
VI  - 173
IP  - 4
4099  - http://www.jimmunol.org/content/173/4/2288.short
4100  - http://www.jimmunol.org/content/173/4/2288.full
SO  - J. Immunol.2004 Aug 15; 173
AB  - A vaccine combining IL-12 and allogeneic mammary carcinoma cells expressing p185neu completely prevents tumor onset in HER-2/neu transgenic BALB/c mice (NeuT mice). The immune protection elicited was independent from CTL activity. We now formally prove that tumor prevention is mainly based on the production of anti-p185neu Abs. In the present studies, NeuT mice were crossed with knockout mice lacking IFN-γ production (IFN-γ−/−) or with B cell-deficient mice (μMT). Vaccination did not protect NeuT-IFN-γ−/− mice, thus confirming a central role of IFN-γ. The block of Ab production in NeuT-μMT mice was incomplete. About one third of NeuT-μMT mice failed to produce Abs and displayed a rapid tumor onset. By contrast, those NeuT-μMT mice that responded to the vaccine with a robust production of anti-p185neu Ab displayed a markedly delayed tumor onset. In these NeuT-μMT mice, the vaccine induced a lower level of IgG2a and IgG3 and a higher level of IgG2b than in NeuT mice. Moreover, NeuT-μMT mice failed to produce anti-MHC class I Abs in response to allogeneic H-2q molecules present in the cell vaccine. These findings show that inhibition of HER-2/neu carcinogenesis depends on cytokines and specific Abs, and that a highly effective vaccine can rescue Ab production even in B cell-deficient mice.