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

用 OK432、TLR7/8 配体和前列腺素 E2 的组合刺激的 3 天单核细胞衍生树突状细胞是癌症免疫治疗的一种有前途的替代方案

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作者:Dag Heiro Yi, Nadine Stetter, Kjerstin Jakobsen, Roland Jonsson, Silke Appel

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.

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