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The induction of antigen-specific CTL by in situ Ad-REIC gene therapy

Gene Therapy volume 23, pages 408–414 (2016)Cite this article

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Abstract

An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA-specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad-REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion.

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Acknowledgements

This work was supported by JSPH KAKENHI Grant Numbers 15H04974, 15H04297 and 26462413.

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Authors and Affiliations

  1. Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Y Ariyoshi, M Watanabe, T Sadahira, T Hirata, M Araki, S Ebara, Y Nasu & H Kumon

  2. Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

    S Eikawa, C Yamazaki & H Udono

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  1. Y Ariyoshi
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  2. M Watanabe
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Corresponding author

Correspondence to Y Nasu.

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Competing interests

Okayama University and Momotaro-Gene Inc. are applying for patents on the Ad-REIC systems. MW, YN and HK are the inventors of the patents and own stock in Momotaro-Gene Inc. The remaining authors declare no conflict of interest.

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Ariyoshi, Y., Watanabe, M., Eikawa, S. et al. The induction of antigen-specific CTL by in situ Ad-REIC gene therapy. Gene Ther 23, 408–414 (2016). https://doi.org/10.1038/gt.2016.7

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