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  • Original Article
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Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF

Cancer Gene Therapy volume 13, pages 510–519 (2006)Cite this article

Abstract

Our previous study showed that DNA vaccination with a plasmid vector encoding a core peptide of mucin1 (PDTRP) provided modest protection against challenge with tumor cells that expressed mucin1 protein. We report here that a DNA vaccine comprising a modified PDTRP plasmid and GM-CSF coding sequence at the C-terminus induced better protection against tumor challenge. The increased protection was directly correlated with a stronger PDTRP-specific immune response induced by the GM-CSF fusion plasmid. The plasmid encoding GM-CSF and the target PDTRP antigen induced a greater PDTRP-specific Th proliferation, antibodies, and cytotoxicity. Interestingly, the modified plasmid vaccine predominantely enhanced the type 2 immune responses manifested by an increased IgG1 to IgG2a antibody ratio and a greater induction of GATA-3 and IL-4 mRNA than that of T-bet and IFN-γ mRNA in spleen cells from vaccinated mice. In addition, protection against tumor challenge in vaccinated mice showed that there was no significant change in mice survival after in vivo CD8+CTL depletion, indicating that antitumor immunity augmented by plasmid encoding GM-CSF and target PDTRP gene vaccine was dominated by Th2 immune response.

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Acknowledgements

We thank Professor Taylor-Papadimitriou (Guy's Hospital, London, UK) for providing the SM-3 antibody and Professor Zanetti (UCSD, CA) for providing the expression plasmids as well as for experimental direction. We also thank Dr Walter J Urba (Robert W Franz Cancer Research Center, Portland, OR) and Dr Hong-Ming Hu (Earle A Chiles Research Institute, Portland, OR) for their help in revision of the manuscript. We thank Xiujuan Zheng for technical assistance. This work was supported partially by the NSFC (30170867), the Major State Basic Research Development Program of the People's Republic of China (2001CB510005), and Science and Technology Commission of Shanghai Municipality (04ZR14012, 04DZ14902).

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  1. Y Chu and M Xia: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, Key Laboratory of Molecular Medicine of Ministry of Education, Shanghai Medical College of Fudan University, Shanghai, China

    Y Chu, M Xia, Y Lin, A Li, Y Wang, R Liu & S Xiong

  2. Immunology Division, E-Institutes of Shanghai Universities, Shanghai, China

    S Xiong

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Correspondence to S Xiong.

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Chu, Y., Xia, M., Lin, Y. et al. Th2-dominated antitumor immunity induced by DNA immunization with the genes coding for a basal core peptide PDTRP and GM-CSF. Cancer Gene Ther 13, 510–519 (2006). https://doi.org/10.1038/sj.cgt.7700913

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