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

John P Graham, The Jackson Laboratory
Pierre Authie, The Jackson Laboratory
A Karolina Palucka, The Jackson Laboratory
Gerard Zurawski


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. Vaccine 2017 Aug 16; 35:4532-4539.