Cancer Immunology, Immunotherapy

, Volume 62, Issue 7, pp 1175–1185 | Cite as

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

  • Sung Yong Lee
  • Tae Heung Kang
  • Jayne Knoff
  • Zhuomin Huang
  • Ruey-Shyang Soong
  • Ronald D. Alvarez
  • Chien-Fu Hung
  • T.-C. Wu
Original Article

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.

Keywords

Cisplatin Vaccine Vaccinia virus Human papillomavirus TA-HPV 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Sung Yong Lee
    • 1
    • 5
  • Tae Heung Kang
    • 1
    • 8
  • Jayne Knoff
    • 1
  • Zhuomin Huang
    • 1
  • Ruey-Shyang Soong
    • 1
    • 6
    • 9
  • Ronald D. Alvarez
    • 7
  • Chien-Fu Hung
    • 1
    • 4
  • T.-C. Wu
    • 1
    • 2
    • 3
    • 4
  1. 1.Department of PathologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  2. 2.Department of Obstetrics and GynecologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  3. 3.Department of Molecular Microbiology and ImmunologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  4. 4.Department of OncologyJohns Hopkins Medical InstitutionsBaltimoreUSA
  5. 5.Department of Internal MedicineKorea University Medical CenterSeoulSouth Korea
  6. 6.Department of General SurgeryChang Gung Memorial HospitalKeelungTaiwan
  7. 7.Department of Obstetrics and GynecologyUniversity of Alabama at BirminghamBirminghamUSA
  8. 8.Department of Immunology, College of MedicineKonkuk UniversityChungjuRepublic of Korea
  9. 9.Chang Gung University, College of MedicineTaoyuanTaiwan

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