3-Day monocyte-derived dendritic cells stimulated with a combination of OK432, TLR7/8 ligand, and prostaglandin E2 are a promising alternative for cancer immunotherapy

Cancer Immunol Immunother. 2018 Oct;67(10):1611-1620. doi: 10.1007/s00262-018-2216-y. Epub 2018 Aug 1.

Abstract

Numerous trials using dendritic cell (DC)-based vaccinations for the treatment of cancer are being carried out. However, an improvement of the quality of DC used is highly warranted. We here generated human monocyte-derived dendritic cells using a 3 day protocol and stimulated the cells using a combination of OK432 (Picibanil), TLR7/8 ligand CL097, and reduced amounts of prostaglandin (PG)E2. We analyzed phenotype, migratory, and T-cell stimulatory capacity compared to a cytokine cocktail consisting of IL-1β, IL-6, TNF, and PGE2. The OK432 cocktail stimulated cells had a similar mature phenotype with upregulated co-stimulatory molecules, HLA-DR and CCR7 as the cytokine cocktail-matured cells and a similar cytokine profile except increased amounts of IL-12p70. Chemotaxis towards CCL19 was reduced compared to the cytokine cocktail, but increased compared to OK432 alone. The T-cell stimulatory capacity was similar to the cytokine cocktail stimulated cells. In conclusion, the OK432 cocktail has the advantage of inducing IL-12p70 production without impairing phenotype or T-cell stimulatory capacity of the cells and might, therefore, be an advantageous alternative to be used in DC-based immunotherapy.

Keywords: Cancer; Dendritic cells; Immunotherapy; OK432; Pro-inflammatory cytokines.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cytokines
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dinoprostone / pharmacology*
  • Humans
  • Immunotherapy*
  • Ligands
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Oxytocics / pharmacology
  • Picibanil / pharmacology*
  • Toll-Like Receptor 7 / metabolism*
  • Toll-Like Receptor 8 / metabolism*

Substances

  • Antineoplastic Agents
  • Cytokines
  • Ligands
  • Oxytocics
  • TLR7 protein, human
  • TLR8 protein, human
  • Toll-Like Receptor 7
  • Toll-Like Receptor 8
  • Picibanil
  • Dinoprostone