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Intratumoral injection of therapeutic HPV vaccinia vaccine following cisplatin enhances HPV-specific antitumor effects

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Despite the conventional treatments of radiation therapy and chemotherapy, the 5-year survival rates for patients with advanced-stage cervical cancers remain low. Cancer immunotherapy has emerged as an alternative, innovative therapy that may improve survival. Here, we utilize a preclinical HPV-16 E6/E7-expressing tumor model, TC-1, and employ the chemotherapeutic agent cisplatin to generate an accumulation of CD11c+ dendritic cells in tumor loci making it an ideal location for the administration of therapeutic vaccines. Following cisplatin treatment, we tested different routes of administration of a therapeutic HPV vaccinia vaccine encoding HPV-16 E7 antigen (CRT/E7-VV). We found that TC-1 tumor-bearing C57BL/6 mice treated with cisplatin and intratumoral injection of CRT/E7-VV significantly increased E7-specific CD8+ T cells in the blood and generated potent local and systemic antitumor immune responses compared to mice receiving cisplatin and CRT/E7-VV intraperitoneally or mice treated with cisplatin alone. We further extended our study using a clinical grade recombinant vaccinia vaccine encoding HPV-16/18 E6/E7 antigens (TA-HPV). We found that intratumoral injection with TA-HPV following cisplatin treatment also led to increased E7-specific CD8+ T cells in the blood as well as significantly decreased tumor size compared to intratumoral injection with wild type vaccinia virus. Our study has strong implications for future clinical translation using intratumoral injection of TA-HPV in conjunction with the current treatment strategies for patients with advanced cervical cancer.

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Acknowledgments

This work was supported by the Cervical Cancer SPORE, P50CA098252, the Head and Neck Cancer SPORE, P50DE019032, and 2RO1 CA114425-06 from the National Institutes of Health/National Cancer Institute.

Conflict of interest

The authors declare that no conflict of interests exist.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins Medical Institutions, CRB II Room 309, 1550 Orleans Street, Baltimore, MD, 21231, USA

    Sung Yong Lee, Tae Heung Kang, Jayne Knoff, Zhuomin Huang, Ruey-Shyang Soong, Chien-Fu Hung & T.-C. Wu

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

    T.-C. Wu

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

    T.-C. Wu

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

    Chien-Fu Hung & T.-C. Wu

  5. Department of Internal Medicine, Korea University Medical Center, Seoul, South Korea

    Sung Yong Lee

  6. Department of General Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan

    Ruey-Shyang Soong

  7. Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL, USA

    Ronald D. Alvarez

  8. Department of Immunology, College of Medicine, Konkuk University, Chungju, Republic of Korea

    Tae Heung Kang

  9. Chang Gung University, College of Medicine, Taoyuan, Taiwan

    Ruey-Shyang Soong

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  1. Sung Yong Lee
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  2. Tae Heung Kang
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  4. Zhuomin Huang
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  6. Ronald D. Alvarez
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  7. Chien-Fu Hung
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  8. T.-C. Wu
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Correspondence to T.-C. Wu.

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Lee, S.Y., Kang, T.H., Knoff, J. et al. Intratumoral injection of therapeutic HPV vaccinia vaccine following cisplatin enhances HPV-specific antitumor effects. Cancer Immunol Immunother 62, 1175–1185 (2013). https://doi.org/10.1007/s00262-013-1421-y

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  • DOI: https://doi.org/10.1007/s00262-013-1421-y

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