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

Gene Ther. 2005 Aug;12(15):1180-6. doi: 10.1038/


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, beta2-microglobulin (beta2m), 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, beta2m, and H-2Kb MHC class I heavy chain (pIRES-E6-beta2m-Kb). Transfection of 293 cells with pIRES-E6-beta2m-Kb can bypass antigen processing and lead to stable presentation of E6 peptide. Furthermore, C57BL/6 mice vaccinated with pIRES-E6-beta2m-Kb 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-beta2m-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Epitopes / genetics
  • Epitopes / immunology
  • Genes, MHC Class I*
  • Genetic Therapy / methods*
  • Humans
  • Immunotherapy, Active / methods*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Neoplasms, Experimental / therapy
  • Oncogene Proteins, Viral / genetics*
  • Papillomavirus Vaccines*
  • Repressor Proteins / genetics*
  • T-Lymphocytes, Cytotoxic / immunology
  • Transplantation, Heterologous


  • Cancer Vaccines
  • E6 protein, Human papillomavirus type 16
  • Epitopes
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • Repressor Proteins