Comparison of adjuvant activity of N- and C-terminal domain of gp96 in a Her2-positive breast cancer model |
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Authors: | Nafiseh Pakravan Zuhair Mohammad Hassan |
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Institution: | (1) Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran;(2) Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Ale-Ahmad Avenue, P.O. Box 14115-331, Tehran, Iran; |
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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. |
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Keywords: | Her2 gp96 terminal domains Regulatory T cells Adjuvant activity Breast cancer Tumor progression |
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