Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity

T. L. Wang, M. Ling, I. M. Shih, T. Pham, S. I. Pai, Z. Lu, R. J. Kurman, D. M. Pardoll, T. C. Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Dendritic cells (DCs) are highly efficient antigen-presenting cells capable of priming both cytotoxic and helper T cells in vivo. Recent studies have demonstrated the potential use of DCs that are modified to carry tumor-specific antigens in cancer vaccines. However, the optimal administration route of DC-based vaccines to generate the greatest anti-tumor effect remains to be determined. This study is aimed at comparing the levels of immune responses and anti-tumor effect generated through different administration routes of DC based vaccination. We chose the E7 gene product of human papillomavirus (HPV) as the model antigen and generated a stable DC line (designated as DC-E7) that constitutively expresses the E7 gene. Among the three different routes of DC-E7 vaccine administration in a murine model, we found that intramuscular administration generated the greatest anti-tumor immunity compared with subcutaneous and intravenous routes of administration. Furthermore, intramuscular administration of DC-E7 elicited the highest levels of E7-specific antibody and greatest numbers of E7-specific CD4+ T helper and CD8+ T cell precursors. Our results indicate that the potency of DC-based vaccines depends on the specific route of administration and that intramuscular administration of E7-transfected DCs generates the most potent E7-specific anti-tumor immunity.

Original languageEnglish (US)
Pages (from-to)726-733
Number of pages8
JournalGene Therapy
Volume7
Issue number9
DOIs
StatePublished - May 2000

Keywords

  • Cervical cancer
  • Dendritic cell
  • E7
  • Human papillomaviruses (HPV)
  • Immunity
  • Vaccines

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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