HER-2 DNA and protein vaccines containing potent Th cell epitopes induce distinct protective and therapeutic antitumor responses in HER-2 transgenic mice.
Overexpression of the growth factor receptor HER-2 (c-erbB-2, neu) has transforming potential and occurs in approximately 20-30% of breast and ovarian cancers. HER-2 is a self Ag, but Abs and T cells specific for HER-2 have been isolated from cancer patients, suggesting HER-2 may be a good target for active immunotherapy. We constructed rat HER-2 DNA and protein vaccines containing potent Th cell epitopes derived from tetanus toxin and studied their potency in two strains of mice transgenic for the rat HER-2 molecule. Vaccination with HER-2 DNA protected nontransgenic mice from tumor challenge, but induced only moderate protection in one of the tumor models. However, vaccination with the modified HER-2 protein resulted in almost complete protection from tumor challenge in both tumor models. This protection could be mediated by Abs alone. In addition, protein vaccination efficiently eliminated pre-established tumors in both models, even when vaccination occurred 9 days after tumor implantation. These data demonstrate the potential of HER-2-based vaccines as therapeutic agents for the treatment of cancers overexpressing HER-2.
Renard
Valéry
V
Pharmexa A/S, Hørsholm, Denmark.
Sonderbye
Lene
L
Ebbehøj
Kirsten
K
Rasmussen
Peter Birk
PB
Gregorius
Klaus
K
Gottschalk
Tine
T
Mouritsen
Søren
S
Gautam
Anand
A
Leach
Dana R
DR
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D000970:Antineoplastic Agents / Q000276:immunology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D007116:Immunization, Passive; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology* / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic