Targeting interferon-alpha to dendritic cells enhances a CD8 + T cell response to a human CD40-targeted cancer vaccine

Vaccine. 2017 Aug 16;35(35 Pt B):4532-4539. doi: 10.1016/j.vaccine.2017.07.032. Epub 2017 Jul 23.

Abstract

Targeting antigens to antigen presenting cells (APC) enhances the potency of recombinant protein CD8+ T cell vaccines. Recent comparisons of recombinant protein-based dendritic cell (DC) targeting vaccines revealed differences in cross-presentation and identified CD40 as a potent human DC receptor target for antigen cross-presentation. Contrary to in vitro-derived monocyte (mo)DC, we found that interferon-alpha (IFNα) stimulation of human blood-derived DC was necessary for an antigen-specific IFNγ CD8+ T cell response to a CD40 targeted cancer vaccine. Importantly, targeting an adjuvant in the form of IFNα to DC increased their potency to elicit antigen-specific production of IFNγ by CD8+ T cells. Thus, we introduce the concept of DC adjuvant targeting to enhance the potency of vaccination.

Keywords: Adjuvant; CD8(+) T cells; Cancer vaccine; Dendritic cells; Interferon-alpha.

MeSH terms

  • Adjuvants, Immunologic*
  • Antigen Presentation
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / genetics
  • CD40 Antigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Cross-Priming
  • Cytokines / analysis
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Humans
  • Interferon-alpha / immunology*
  • Neoplasms / immunology
  • Neoplasms / prevention & control
  • Vaccination
  • Vaccine Potency

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • CD40 Antigens
  • Cancer Vaccines
  • Cytokines
  • Interferon-alpha