DNA vaccination with full-length or truncated Neu induces protective immunity against the development of spontaneous mammary tumors in HER-2/neu transgenic mice

Genetic immunization against tumor antigens is an effective way to induce a n immune response able to oppose cancer progression. Overexpression of HER- 2/neu can lead to neoplastic transformation and has been found in many huma n primary breast cancers. We constructed DNA expression vectors encoding th e full-length neu oncogene of rat cDNA (pCMV-NeuNT), the neu extracellular domain (pCMV-ECD), or the neu extracellular and transmembrane domains (pCMV -ECD-TM). We evaluated whether i.m. injection of these plasmids induces pro tection against the development of mammary tumors occurring spontaneously i n FVB/N neutransgenic mice. We found that pCMV-ECD-TM induced the best prot ection, whereas both pCMV-ECD and pCMV-NeuNT were less effective. The coinj ection with a bicistronic vector for murine IL-12 increased the efficacy of pCMV-ECD and pCMV-NeuNT plasmids, and led to the same protection obtained with pCMV-ECD-TM alone. Anti-NeuECD antibodies were detected in pCMV-ECD-TM vaccinated mice and, after coinjection with pCMV-IL12 plasmids, they appea red also in animals immunized with pCMV-ECD. Our data demonstrate the effec tiveness of DNA vaccination using truncated Neu plasmids in inducing antitu mor protection in a spontaneous mammary tumor model.