Eradication of established HPV 16-expressing tumors by a single administration of a vaccine composed of a liposome-encapsulated CTL-T helper fusion peptide in a water-in-oil emulsion

Pirouz Daftarian, Marc Mansour, Anita C. Benoit, Bill Pohajdak, David W. Hoskin, Robert G. Brown, W. Martin Kast

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Human papillomavirus (HPV)-induced cervical cancer is the second most common cancer among women worldwide with half a million new cases per year. Despite the encouraging development of a preventive vaccine for HPV, a therapeutic vaccine for cervical cancer or pre-cancerous lesions remains a high priority. The preclinical study reported here used VacciMax® (VM) to deliver a peptide-based vaccine composed of an HPV 16 E7-derived cytotoxic T lymphocyte (CTL) epitope fused to the T helper epitope PADRE (FP) and combined with CpG or lipopeptide adjuvant. In the study, C57BL/6 mice received 0.5 million HPV 16-expressing C3 tumor cells. Mice were inoculated post-tumor challenge with a single s.c. injection of FP-CpG-VM on either day 4, 5, 6, 9, or 14. All mice that received the FP-CpG-VM vaccine were tumor-free to day 130 when the experiment was terminated. In contrast, only a minority of mice that received a control vaccine were tumor-free on day 60. Cytotoxicity assays, ELISPOT and intracellular staining for interferon (IFN)-γ showed the immune response was specific for the selected CTL epitope. All mice that received the FP-CpG-VM vaccine remained tumor-free when re-challenged with 6 million C3 cells. Cytotoxicity assays 4 months post-challenge showed that only splenocytes from mice inoculated with the FP-CpG-VM vaccine had high lysis activity. These results indicate that VacciMax® causes a rapid, robust, durable and therapeutic CTL response to HPV 16 E7 protein expressing tumors.

Original languageEnglish (US)
Pages (from-to)5235-5244
Number of pages10
JournalVaccine
Volume24
Issue number24
DOIs
StatePublished - Jun 12 2006

Keywords

  • Cervical cancer
  • Human papillomavirus
  • Immunotherapy
  • Liposome
  • Peptide
  • Theraputic
  • Vaccine

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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