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Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice

Gene Therapy volume 15, pages 1176–1183 (2008)Cite this article

Abstract

Multimodality treatments that combine conventional cancer therapies with antigen-specific immunotherapy have emerged as promising approaches for the control of cancer. In the current study, we have explored the effect of doxorubicin on the antigen-specific immune responses generated in mice vaccinated with calreticulin (CRT)/E6 and/or Ii-PADRE DNA. We observed that pretreatment with doxorubicin suppressed the E6-specific CD8+ T-cell immune responses generated by CRT/E6 DNA vaccination in vaccinated mice. In contrast, pretreatment with doxorubicin enhanced the PADRE-specific CD4+ T-cell immune responses generated by Ii-PADRE DNA vaccination. Furthermore, coadministration of Ii-PADRE DNA could not only reverse the suppression, but also enhanced the E6-specific CD8+ T-cell responses in CRT/E6-vaccinated mice pretreated with doxorubicin. Finally, treatment with doxorubicin followed by CRT/E6 combined with Ii-PADRE DNA vaccination led to enhanced antitumor effects and prolonged survival in TC-1 tumor-bearing mice. The clinical implications of the current study are discussed.

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Acknowledgements

This work was supported by the Flight Attendant Medical Research Institute and National Cancer Institute SPORE in Cervical Cancer P50 CA098252 and the 1 RO1 CA114425-01.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    D Kim, A Monie, Y-C Tsai, L He, C-F Hung & T-C Wu

  2. Department of Anatomy, Chung-Ang University College of Medicine, Dongjak-Gu, Seoul, South Korea

    D Kim

  3. Department of Biostatistics, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    M-C Wang

  4. Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    C-F Hung & T-C Wu

  5. Department of Obstetrics and Gynecology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

  6. Department of Molecular Microbiology and Immunology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    T-C Wu

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  1. D Kim
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  2. A Monie
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  3. Y-C Tsai
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  4. L He
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Correspondence to T-C Wu.

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Kim, D., Monie, A., Tsai, YC. et al. Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice. Gene Ther 15, 1176–1183 (2008). https://doi.org/10.1038/gt.2008.79

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