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Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors

Cancer Gene Therapy volume 19, pages 637–643 (2012)Cite this article

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Abstract

Interferon-alpha (IFN-α) has strong antitumor effects, and IFN-α gene therapy has been used clinically against some cancers. In this study, we evaluated the efficacy of the combination of IFN-α-transduced tumor cell vaccines and programmed cell death 1 (PD-1) blockade, and investigated the mechanisms of the antitumor effects of the combined therapy. A poorly immunogenic murine colorectal cancer cell line, MC38, was transduced to overexpress IFN-α. In a therapeutic model, parental tumor-bearing mice were inoculated with MC38-IFNα cells and an anti-PD-1 antagonistic antibody. Analyses of immunohistochemistry and tumor-specific lysis were performed. The outgrowth of the established tumors was significantly reduced in mice treated with the combination of IFN-α and anti-PD-1. Immunohistochemical analyses of the therapeutic model showed marked infiltration of CD4+ cells and CD8+ cells in the established MC38 tumors of mice treated with both IFN-α and anti-PD-1. Significant tumor-specific cytolysis was detected when splenocytes of mice that were treated with both IFN-α and anti-PD-1 were used as effector cells. These results suggest that blockade of the PD-1 PD-ligand enhanced the Th1-type antitumor immune responses induced by IFN-α. The combination of IFN-α gene-transduced tumor cell vaccines and PD-1 blockade may be a possible candidate for a cancer vaccine for clinical trials.

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Acknowledgements

We thank Ms Tomoe Shimazaki and Ms Hisako Nozawa for technical assistance. This study was supported in part by a Grant-in-Aid for Young Scientists (B) from the Ministry of Education, Culture, Sports, Science and Technology of Japan for JE; a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and a grant from the Ministry of Health, Labor, and Welfare of Japan for KH.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan

    R Omori, J Eguchi, K Hiroishi, S Ishii, A Hiraide, M Sakaki, H Doi, A Kajiwara, T Ito & M Imawari

  2. Promotion Center of Pharmaceutical Education, Showa University School of Pharmacy, Shinagawa-ku, Tokyo, Japan

    M Kogo

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  1. R Omori
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  2. J Eguchi
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Correspondence to J Eguchi.

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Omori, R., Eguchi, J., Hiroishi, K. et al. Effects of interferon-α-transduced tumor cell vaccines and blockade of programmed cell death-1 on the growth of established tumors. Cancer Gene Ther 19, 637–643 (2012). https://doi.org/10.1038/cgt.2012.42

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