Human dendritic cells activated and loaded with tumorantigen through mRNA electroporation as melanoma vaccine.

Data has been obtained on TriMix DCs co-electroporated with whole tumorantigen encoding mRNA.

A critical factor determining the effectiveness of currently used dendritic cell (DC)-based vaccines, is the DC’s activation or maturation status. We have shown recently that the T cell stimulatory capacity of DCs pulsed with tumorantigen-derived peptides can be considerably increased by activating the DCs through electroporation with CD40L, CD70 and constitutively active TLR4 encoding mRNA (TriMix DCs). Here, we investigate whether TriMix DCs can be co-electroporated with whole tumorantigen encoding mRNA.
The T cell stimulatory capacity of TriMix DCs pulsed with the immunodominant MelanA-A2 peptide and of TriMix DCs co-electroporated with MelanA mRNA was compared in vitro. TriMix DCs were also co-electroporated with Mage-A3, Mage-C2, Tyrosinase or gp100 mRNA. The capacity of these DCs to stimulate tumorantigen-specific T cells in melanoma patients, was investigated both in vitro prior to vaccination and after DC-vaccination.
Like peptide-pulsed TriMix DCs, TriMix DCs co-electroporated with MelanA mRNA are very potent in inducing MelanA-specific CD8+ T cells. These T cells have an activated phenotype, show cytolytic capacity and produce inflammatory cytokines in response to specific stimulation. TriMix DCs co-electroporated with Tyrosinase are able to stimulate Tyrosinase-specific CD8+ T cells in vitro from the blood of non-vaccinated melanoma patients. Furthermore, TriMix DCs co-electroporated with Mage-A3, Mage-C2 or Tyrosinase are able to induce antigen-specific CD8+ T cells through vaccination.
TriMix DCs co-electroporated with whole tumorantigen mRNA stimulate antigen-specific T cells both in vitro and through vaccination and thus form a promising new approach for anti-tumor immunotherapy.

• organism type
• Homo sapiens

• cell type
• T cell,
• dendritic cell

• molecule type
• peptide,
• CD8,
• CD70,
• CD40 ligand,
• Toll like receptor 4,
• tyrosinase,
• Melan A,
• messenger RNA

created over 14 years ago (17 December 2009)    last modified over 11 years ago (21 January 2013)   [ RDF ]   [ RelFinder ]