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 an immune response able to oppose cancer progression. Overexpression of HER-2/neu can lead to neoplastic transformation and has been found in many human primary breast cancers. We constructed DNA expression vectors encoding the 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 protection against the development of mammary tumors occurring spontaneously in FVB/N neu-transgenic mice. We found that pCMV-ECD-TM induced the best protection, whereas both pCMV-ECD and pCMV-NeuNT were less effective. The coinjection 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 appeared also in animals immunized with pCMV-ECD. Our data demonstrate the effectiveness of DNA vaccination using truncated Neu plasmids in inducing antitumor protection in a spontaneous mammary tumor model.
Amici
A
A
General Physiology (Laboratory of Genetic Immunization), Department of Biology MCA, University of Camerino, Camerino, Italy.
Smorlesi
A
A
Noce
G
G
Santoni
G
G
Cappelletti
P
P
Capparuccia
L
L
Coppari
R
R
Lucciarini
R
R
Petrelli
C
C
Provinciali
M
M
D000818:Animals; D000912:Antibodies, Neoplasm / Q000097:blood; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007273:Injections, Intramuscular; D018664:Interleukin-12 / Q000235:genetics; D015674:Mammary Neoplasms, Animal / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000912:Antibodies, Neoplasm; D018664:Interleukin-12; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA