Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy

Luciene Lopes, Kate Fletcher, Yasuhiro H Ikeda, Mary Collins

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Therapeutic cancer vaccines need to stimulate a refractory immune system to make an effective anti-tumour response. We have explored the use of lentiviral vectors to deliver tumour antigen genes to dendritic cells (DC) as a possible mechanism of immune stimulation. Direct injection of a lentiviral vector encoding the melanoma antigen NY-ESO-1 in HLA-A2 transgenic mice primed NY-ESO-1-specific CD8+ cells that could be expanded by boosting with an NY-ESO-1 vaccinia virus. The expanded cells could kill NY-ESO-1157-165 peptide-pulsed targets in vivo. In order to examine the priming step directly, we constructed another lentiviral vector expressing the melanoma antigen Melan-A (MART-1). Here we show that Melan-A protein is also efficiently expressed after transduction of human DC cultured from peripheral blood mononuclear cells. When these transduced DC are co-cultured with autologous naïve T cells, they cause the expansion of cells that recognise the HLA-A2 restricted Melan-A27-35 epitope. The expanded cells are functional in that they release IFN-γ upon antigen stimulation. Melan-A lentiviral vector transduced DC caused a similar level of naïve T-cell expansion to Melan-A27-35 peptide-pulsed DC in four experiments using different HLA-A2 positive donors. These data suggest that a vaccine based either on DC transduced with a lentiviral vector ex vivo, or on direct lentiviral vector injection, should be assessed in a phase I clinical trial.

Original languageEnglish (US)
Pages (from-to)1011-1016
Number of pages6
JournalCancer Immunology, Immunotherapy
Volume55
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

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Neoplasm Antigens
Dendritic Cells
MART-1 Antigen
HLA-A2 Antigen
Melanoma-Specific Antigens
T-Lymphocytes
Peptides
Clinical Trials, Phase I
Cancer Vaccines
Injections
Vaccinia virus
Transgenic Mice
Epitopes
Immune System
Blood Cells
Vaccines
Antigens
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

Cite this

Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy. / Lopes, Luciene; Fletcher, Kate; Ikeda, Yasuhiro H; Collins, Mary.

In: Cancer Immunology, Immunotherapy, Vol. 55, No. 8, 08.2006, p. 1011-1016.

Research output: Contribution to journalArticle

Lopes, Luciene ; Fletcher, Kate ; Ikeda, Yasuhiro H ; Collins, Mary. / Lentiviral vector expression of tumour antigens in dendritic cells as an immunotherapeutic strategy. In: Cancer Immunology, Immunotherapy. 2006 ; Vol. 55, No. 8. pp. 1011-1016.
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