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Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures

Gene Therapy volume 21, pages 106–114 (2014)Cite this article

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Abstract

For successful clinical tumor immunotherapy outcomes, strong immune responses against tumor antigens must be generated. Cell-based vaccines compromise one strategy with which to induce appropriate strong immune responses. Previously, we established a natural killer T-cell (NKT) ligand-loaded, adenoviral vector-transduced B-cell-based anticancer cellular vaccine. To enhance tumor antigen delivery to B cells, we established a modified adenoviral vector (Ad-k35) that encoded a truncated form of the breast cancer antigen Her2/neu (Ad-k35HM) in which fiber structure was substituted with adenovirus serotype 35. We observed increased tumor antigen expression with Ad-k35HM in both human and murine B cells. In addition, an Ad-k35HM-transduced B-cell vaccine elicited strong antigen-specific cellular and humoral immune responses that were further enhanced with the additional loading of soluble NKT ligand KBC009. An Ad-k35HM-transduced, KBC009-loaded B-cell vaccine efficiently suppressed the in vivo growth of established tumors in a mouse model. Moreover, the vaccine elicited human leukocyte antigen (HLA)-A2 epitope-specific cytotoxic T-cell responses in B6.Cg (CB)-Tg (HLA-A/H2-D) 2Enge/Jat mice. These findings indicated that the Ad-k35 could be appropriate for the preclinical and clinical development of B-cell-based anticancer immunotherapies.

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Acknowledgements

This work was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health and Welfare (0720500) and the World Class University Program (Grant R31-2008-000-10103-0) of the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology.

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Authors and Affiliations

  1. Laboratory of Immunology, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Korea

    E-K Kim, M-J Chae, Y-J Park & C-Y Kang

  2. WCU Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea

    H-S Seo, I-S Jeon, B-Y Song & C-Y Kang

  3. Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea

    H M Ahn & C-O Yun

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Kim, EK., Seo, HS., Chae, MJ. et al. Enhanced antitumor immunotherapeutic effect of B-cell-based vaccine transduced with modified adenoviral vector containing type 35 fiber structures. Gene Ther 21, 106–114 (2014). https://doi.org/10.1038/gt.2013.65

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