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Adjuvant activity of GP96 C-terminal domain towards Her2/neu DNA vaccine is fusion direction-dependent

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Cell Stress and Chaperones Aims and scope

Abstract

The Her2 is one of tumor-associated antigens (TAA), regarded as an ideal target of immunotherapy. DNA encoding full-length or truncated rat Her2/neu have shown protective and therapeutics potentials against Her2/neu-expressing mammary tumors. However, the efficacy of active vaccination is limited since Her2 is a self-tolerated antigen. Hence, new strategies are required to enhance both the quality and quantity of the immune response against Her2-expressing tumors. Many studies have used Her2/neu gene with cytokine or other molecules involved in regulation of immune response to enhance the potency of Her2/neu DNA vaccines. Some studies fused adjuvant gene to C-terminal domain of Her2/neu gene, while others fused the adjuvant gene N-terminally to Her2/neu gene, but no comparison on how direction of fusion could affect efficiency of DNA vaccine has ever been made. Based on previous reports demonstrating potent adjuvant activity of gp96 C-terminal domain, we chose it as adjuvant. The aim of this study was to investigate if direction of fusion could affect adjuvant activity of gp96 C-terminal domain or potency of Her2/neu DNA vaccination. To do so, we fused C-terminal domain of gp96 to downstream or C-terminal end of transmembrane and extracellular domain (TM+ECD) of rat Her2/neu and resultant immune response to DNA vaccination was evaluated. The results were compared with that of N-terminally fusion of gp96 C-terminal domain to TM+ECD of rat Her2/neu. Our results revealed that adjuvant activity of gp96 C-terminal domain is enhanced when fused N-terminally to TM+ECD of rat Her2/neu. It suggests that adjuvant activity of gp96 C-terminal domain towards Her2/neu is fusion direction-dependent.

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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. Our gratitude is also conveyed towards Dr. Majid Tebyanian, Dr. Mehdi Mahdavi (Tarbiat Modares University, Tehran, Iran), and Dr. Farhad Riazi (Pasteur Institute, Tehran, Iran) for their 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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  1. Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Ale-Ahmad Avenue, P.O. Box 14115-331, Tehran, Iran

    Nafiseh Pakravan, Seyed Mahmoud Hashemi & Zuhair Mohammad Hassan

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  1. Nafiseh Pakravan
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  2. Seyed Mahmoud Hashemi
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  3. Zuhair Mohammad Hassan
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Correspondence to Zuhair Mohammad Hassan.

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Pakravan, N., Hashemi, S.M. & Hassan, Z.M. Adjuvant activity of GP96 C-terminal domain towards Her2/neu DNA vaccine is fusion direction-dependent. Cell Stress and Chaperones 16, 41–48 (2011). https://doi.org/10.1007/s12192-010-0219-5

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  • DOI: https://doi.org/10.1007/s12192-010-0219-5

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