Activity of DNA vaccines encoding self or heterologous Her-2/neu in Her-2 or neu transgenic mice.
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.
Jacob
Jennifer
J
Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Radkevich
Olga
O
Forni
Guido
G
Zielinski
John
J
Shim
David
D
Jones
Richard F
RF
Wei
Wei-Zen
WZ
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D045744:Cell Line, Tumor; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology*
D000941:Antigens; D019496:Cancer Vaccines; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA