Abstract
Heat-shock proteins have biochemical and immunological roles in chaperoning/signaling and activation of innate and adaptive immune responses, respectively. Their effect on the immune response is due to a phenomenon known as cross-priming of antigen, in which exogenous antigens are presented via MHC class I by antigen presenting cells. GP96 exerts adjuvant activity with some viral and bacterial antigens when applied in the form of a DNA vaccine. In this study, animals with Her2-expressing tumors were vaccinated by co-administration of GP96+ Her2/neu DNA vaccines. Analyses of the immune response, 2 weeks after the last immunization revealed decreased CD4+ CD25+ Foxp3+ naturally occurring regulatory T cells (Tregs) at the tumor site and increased IFN-γ/IL-4 level. Nevertheless, the graph of tumor size demonstrated a bi-phasic pattern in which partial control of tumor progression initially occurred, but finally its effectiveness was inversely affected by tumor size.
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Acknowledgments
We are grateful to Professor Federica Cavallo (Turin University Italy) and Professor Brian Seed (Harvard Medical School, USA) for kindly providing us with rat Her2 and human gp96 genes. We sincerely thank Dr Majid Tebyanian (Tarbiat Modares University, Iran) for his expert advice on flow cytometry results. Our gratitude is also conveyed towards Dr Farhad Riazi (Pasteur Institute of Iran) for his expert advice during the work.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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Pakravan, N., Langroudi, L., Hajimoradi, M. et al. Co-administration of GP96 and Her2/neu DNA vaccine in a Her2 breast cancer model. Cell Stress and Chaperones 15, 977–984 (2010). https://doi.org/10.1007/s12192-010-0208-8
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DOI: https://doi.org/10.1007/s12192-010-0208-8