Autologous dendritic cell (DC)
therapy is an experimental cellular
immunotherapy that is safe and immunogenic in patients with advanced
melanoma. In an attempt to further improve the therapeutic responses, we treated 15 patients with
melanoma, with autologous monocyte-derived immature DC electroporated with
mRNA encoding
CD40 ligand (
CD40L), CD70 and a constitutively active TLR4 (caTLR4) together with
mRNA encoding a
tumor-associated
antigen (TAA; respectively gp100 or
tyrosinase). In addition, DC were pulsed with
keyhole limpet hemocyanin (KLH) that served as a control
antigen. Production of this DC
vaccine with high cellular viability, high expression of co-stimulatory molecules and MHC class I and II and production of IL-12p70, was feasible in all patients. A vaccination cycle consisting of three vaccinations with up to 15×106 DC per vaccination at a biweekly interval, was repeated after 6 and 12 months in the absence of
disease progression.
mRNA-optimized DC were injected intranodally, because of low CCR7 expression on the DC, and induced de novo immune responses against control
antigen. T cell responses against
tyrosinase were detected in the skin-test infiltrating lymphocytes (SKIL) of two patients. One mixed
tumor response and two durable
tumor stabilizations were observed among 8 patients with evaluable disease at baseline. In conclusion, autologous
mRNA-optimized DC can be safely administered intranodally to patients with metastatic
melanoma but showed limited immunological responses against
tyrosinase and gp100.