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

• Published in: Vaccine Vol. 35; no. 35; pp. 4532 - 4539
• Main Authors: Graham, John P., Authie, Pierre, Karolina Palucka, A., Zurawski, Gerard
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 16-08-2017; Elsevier Limited
• Subjects: Adenomatous polyposis coli; Adjuvant; Antigen-presenting cells; Antigens; Blood; Cancer; Cancer vaccine; Cancer vaccines; CD40 antigen; CD8 antigen; CD8+ T cells; Cloning; Cytokines; Dendritic cells; Immunoglobulins; Immunotherapy; Interferon; Interferon-alpha; Ligands; Lymphocytes; Lymphocytes T; Monocytes; Proteins; Stimulation; T cell receptors; Vaccines; α-Interferon; APCs; Cancer vaccine; CD8+ T cells; Dendritic cells; DCs; Interferon-alpha; pDCs; Adjuvant; FACS; cDCs; CD8(+) T cells
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2017.07.032

•An antigen-specific CD8+ T cell response to a CD40-targeted cancer antigen vaccine requires IFNα stimulation of DC.•CD141+ cDC are most potent at inducing these IFNα-dependent responses.•Targeting IFNα to DC-expressed DEC-205 enhances the potency of IFNα.
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.