Timely DNA vaccine combined with systemic IL-12 prevents parotid carcinomas before a dominant-negative p53 makes their growth independent of HER-2/neu expression.
Double transgenic mice overexpressing the transforming rat HER-2/neu oncogene and the mutated p53, with both dominant-negative and a gain-of-function properties, display early aggressive and metastasizing parotid tumors. Multiple acinar and ductal hyperplasia foci overexpressing the HER-2/neu gene product are evident at wk 5 and progress to poorly differentiated carcinoma by wk 7. Mice die before wk 18 with invasive carcinomas and multiple metastases that no longer express HER-2/neu. A combination of repeated electroporations of plasmids coding for the extracellular and transmembrane domains of the rat HER-2/neu receptor with systemic IL-12 administrations started when the parotids that present diffuse hyperplasia protected all female and 50% of the male mice until the close of the experiment at wk 40. This combined treatment began when multifocal in situ carcinomas that were already present cured 33% of the females and 25% of the males. The most prominent immunologic features associated with the antitumor protection were the production of high titers of anti-HER-2/neu Abs and the nonappearance of cell-mediated cytotoxic reactivity. In conclusion, anti-HER-2/neu vaccination combined with systemic IL-12 control parotid carcinomas as far as p53 mutation makes their growth independent of HER-2/neu expression.
Pannellini
Tania
T
Aging Research Center, CeSi, G. d'Annunzio University Foundation, Chieti, Italy.
Spadaro
Michela
M
Di Carlo
Emma
E
Ambrosino
Elena
E
Iezzi
Manuela
M
Amici
Augusto
A
Lollini
Pier Luigi
PL
Forni
Guido
G
Cavallo
Federica
F
Musiani
Piero
P
D016475:3T3 Cells; D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D002277:Carcinoma / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D018664:Interleukin-12 / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010307:Parotid Neoplasms / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; D019444:Vaccines, DNA