title: Comparison of adjuvant activity of N- and C-terminal domain of gp96 in a Her2-positive breast cancer model.
abstract: It has been frequently reported that gp96 acts as a strong biologic adjuvant. Some studies have even investigated adjuvant activity of the gp96 C- or N-terminal domain. The controversy surrounding adjuvant activity of gp96 terminal domains prompted us to compare adjuvant activity of gp96 C- or N-terminal domain toward Her2/neu, as DNA vaccine in a Her2/neu-positive breast cancer model. To do so, mice were immunized with DNA vaccine consisting of transmembrane and extracellular domain (TM + ECD) of rat Her2/neu alone or fused to N- or C-terminal domain of gp96. Treatment with Her2/neu fused to N-terminal domain of gp96 resulted in tumor progression, compared to the groups vaccinated with pCT/Her2 or pHer2. Immunological examination revealed that treatment with Her2/neu fused to N-terminal domain of gp96 led to significantly lower survival rates, higher interferon-γ secretion, and induced infiltration of CD4(+)/CD8(+) cells to the tumor site. However, it could not induce cytotoxic T lymphocyte activity, did not decrease regulatory T cell percentage at the tumor site, and eventually led to tumor progression. Our results reveal that gp96 N-terminal domain does not have adjuvant activity toward Her2/neu. It is also proposed that adjuvant activity and the resultant immune response of gp96 terminal domains may be directed by the antigen applied.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Iran.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Pakravan
authors.forename: Zuhair Mohammad
authors.initials: ZM
authors.lastname: Hassan
mesh_terms: D000277:Adjuvants, Pharmaceutic; D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D000277:Adjuvants, Pharmaceutic; D019496:Cancer Vaccines; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA; C053387:endoplasmin