Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope

C. H. Huang, S. Peng, L. He, Y. C. Tsai, D. A.K. Boyd, T. H. Hansen, T. C. Wu, C. F. Hung

Research output: Contribution to journalArticle

Abstract

The potency of DNA vaccines may be affected by the efficiency of intracellular processing and MHC class I presentation of encoded antigens. Since a single-chain trimer (SCT) composed of peptide, β2-microglobulin (β2m), and MHC class I heavy chain has been shown to bypass antigen processing and lead to stable presentation of peptides, we investigated the efficacy of a DNA vaccine encoding a SCT composed of an immunodominant CTL epitope of human papillomavirus type 16 (HPV-16) E6 antigen, β2m, and H-2Kb MHC class I heavy chain (pIRES-E6-β2m-Kb). Transfection of 293 cells with pIRES-E6-β2m-Kb can bypass antigen processing and lead to stable presentation of E6 peptide. Furthermore, C57BL/6 mice vaccinated with pIRES-E6-β2m-K9 exhibited significantly increased E6 peptide-specific CD8+ T-cell immune responses compared to mice vaccinated with DNA encoding wild-type E6. Most importantly, 100% of mice vaccinated with pIRES-E6-β2m-Kb DNA were protected against a lethal challenge of E6-expressing TC-1 tumor cells. In contrast, all mice vaccinated with wild-type E6 DNA or control plasmid DNA grew tumors. Our data indicate that a DNA vaccine encoding a SCT can lead to stable enhanced MHC class I presentation of encoded antigenic peptide and may be useful for improving DNA vaccine potency to control tumors or infectious diseases.

Original languageEnglish (US)
Pages (from-to)1180-1186
Number of pages7
JournalGene Therapy
Volume12
Issue number15
DOIs
StatePublished - Aug 1 2005

Keywords

  • DNA vaccine
  • HPV-16 E6
  • Immunotherapy
  • Single-chain trimer
  • Tumor immunology

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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