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

Chuan Hsiang Huang, Shiwen Peng, L. He, Y. C. Tsai, D. A K Boyd, T. H. Hansen, Tzyy Choou Wu, Chien-Fu 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 2005

Fingerprint

Immunodominant Epitopes
DNA Vaccines
Human papillomavirus 16
Immunotherapy
Antigen Presentation
Peptides
Vaccine Potency
DNA
Neoplasms
H-2 Antigens
Inbred C57BL Mouse
Transfection
Communicable Diseases
Plasmids
T-Lymphocytes

Keywords

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

ASJC Scopus subject areas

  • Genetics

Cite this

Cancer immunotherapy using a DNA vaccine encoding a single-chain trimer of MHC class I linked to an HPV-16 E6 immunodominant CTL epitope. / Huang, Chuan Hsiang; Peng, Shiwen; He, L.; Tsai, Y. C.; Boyd, D. A K; Hansen, T. H.; Wu, Tzyy Choou; Hung, Chien-Fu.

In: Gene Therapy, Vol. 12, No. 15, 08.2005, p. 1180-1186.

Research output: Contribution to journalArticle

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