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

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.
AuthorsSung Yong Lee, Tae Heung Kang, Jayne Knoff, Zhuomin Huang, Ruey-Shyang Soong, Ronald D Alvarez, Chien-Fu Hung, T-C Wu
JournalCancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 62 Issue 7 Pg. 1175-85 (Jul 2013) ISSN: 1432-0851 [Electronic] Germany
PMID23615841 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antigens, CD11c
  • Antineoplastic Agents
  • Cancer Vaccines
  • E6 protein, Human papillomavirus type 16
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Repressor Proteins
  • oncogene protein E7, Human papillomavirus type 16
  • Cisplatin
Topics
  • Animals
  • Antigens, CD11c (metabolism)
  • Antineoplastic Agents (therapeutic use)
  • CD8-Positive T-Lymphocytes (immunology)
  • Cancer Vaccines (administration & dosage, immunology)
  • Cisplatin (therapeutic use)
  • Dendritic Cells (immunology)
  • Female
  • Human papillomavirus 16 (immunology)
  • Injections, Intralesional
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral (immunology, metabolism)
  • Papillomavirus E7 Proteins (immunology, metabolism)
  • Papillomavirus Infections (immunology, therapy)
  • Papillomavirus Vaccines (administration & dosage, immunology, therapeutic use)
  • Repressor Proteins (immunology, metabolism)
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms (immunology, therapy)
  • Vaccinia virus (immunology)

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