To assess the efficacy of self versus heterologous ErbB-2 vaccines, the reactivity to human and rat ErbB-2 (Her-2 and neu, respectively) DNA vaccines were tested in normal, Her-2 or neu transgenic mice. When immunized with either Her-2 or neu DNA, normal BALB/c and C57BL/6 mice produced cross-reactive T cells, but only antigen specific antibodies. In Her-2 Tg mice, weak to no anti-Her-2 response was induced by either self Her-2 or heterologous neu DNA, demonstrating profound tolerance to Her-2 and the inability to induce anti-Her-2 immunity with either vaccine. In NeuT mice, vaccination with self neu but not heterologous Her-2 DNA induced anti-neu antibodies and delayed spontaneous tumorigenesis. Both neu and Her-2 DNA induced anti-neu T cell response, but depletion of CD8 T cells did not change the delay in tumorigenesis. Therefore, in NeuT mice, both self and heterologous DNA activated anti-neu T cells, although T cell response did not reach sufficient level to suppress spontaneous tumorigenesis. Rather, induction of anti-neu antibodies by self neu DNA is associated with the delay in spontaneous tumor growth. Overall, NeuT mice were more responsive to DNA vaccination than Her-2 Tg mice and this may be associated with the continuous production of neu by the 10 mammary glands undergoing tumor progression.

Activity of DNA vaccines encoding self or heterologous Her-2/neu in Her-2 or neu transgenic mice

FORNI, Guido;
2006-01-01

Abstract

To assess the efficacy of self versus heterologous ErbB-2 vaccines, the reactivity to human and rat ErbB-2 (Her-2 and neu, respectively) DNA vaccines were tested in normal, Her-2 or neu transgenic mice. When immunized with either Her-2 or neu DNA, normal BALB/c and C57BL/6 mice produced cross-reactive T cells, but only antigen specific antibodies. In Her-2 Tg mice, weak to no anti-Her-2 response was induced by either self Her-2 or heterologous neu DNA, demonstrating profound tolerance to Her-2 and the inability to induce anti-Her-2 immunity with either vaccine. In NeuT mice, vaccination with self neu but not heterologous Her-2 DNA induced anti-neu antibodies and delayed spontaneous tumorigenesis. Both neu and Her-2 DNA induced anti-neu T cell response, but depletion of CD8 T cells did not change the delay in tumorigenesis. Therefore, in NeuT mice, both self and heterologous DNA activated anti-neu T cells, although T cell response did not reach sufficient level to suppress spontaneous tumorigenesis. Rather, induction of anti-neu antibodies by self neu DNA is associated with the delay in spontaneous tumor growth. Overall, NeuT mice were more responsive to DNA vaccination than Her-2 Tg mice and this may be associated with the continuous production of neu by the 10 mammary glands undergoing tumor progression.
2006
240
96
106
JACOB J; RADKEVICH O; FORNI G; ZIELINSKI J; SHIM; D; JONES RF
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/37320
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