Immunogenicity of a recombinant lentiviral vector carrying human telomerase tumor antigen in HLA-B*0702 transgenic mice

Vaccine. 2010 Aug 31;28(38):6374-81. doi: 10.1016/j.vaccine.2010.06.071. Epub 2010 Jul 21.

Abstract

Over expression of telomerase represents a hallmark of cancer cells and the induction of T cell immunity against this universal tumor antigen have gained promising interest for anticancer immunotherapy. In this study we evaluated a recombinant lentiviral vector expressing the human telomerase reverse transcriptase (lv-hTERT) vaccination in the humanized HLA-B*0702 transgenic (HLA-B7 Tg) mice. A single lv-hTERT vector immunization induces potent and broad HLA-B7-restricted CTL responses against hTERT. Unlike conventional hTERT peptide or DNA immunization, the lv-hTERT vector triggers high and sustained IFN-gamma producing CD8(+) T cell responses in HLA-B7 Tg mice. The avidity and in vivo cytotoxicity of CD8(+) T cells were stronger in lv-hTERT vector-immunized mice than in hTERT peptide or DNA vaccinated groups. The study also showed that the use of prime-boost vaccination drastically improved the magnitude and strength of lentivector-primed CD8(+) T cells. Our data indicated that lentiviral delivery of hTERT is suitable for enhancing cellular immunity against hTERT and offers a promising alternative for telomerase-based cancer vaccine.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Cell Line
  • Female
  • Genetic Vectors / immunology*
  • HLA-B Antigens / genetics
  • HLA-B7 Antigen
  • Humans
  • Immunity, Cellular
  • Interferon-gamma / immunology
  • Lentivirus / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • T-Lymphocytes, Cytotoxic / immunology*
  • Telomerase / immunology*
  • Vaccines, DNA / immunology
  • Vaccines, Subunit / immunology

Substances

  • Cancer Vaccines
  • HLA-B Antigens
  • HLA-B*07:02 antigen
  • HLA-B7 Antigen
  • Vaccines, DNA
  • Vaccines, Subunit
  • Interferon-gamma
  • TERT protein, human
  • Telomerase