DERMA-ER-DC 06 trial: RNA-based DC vaccine

Design of this trial: sequential adaptive design, 2nd cohort, mature DC transfected with RNA encoding MelanA, Mage3 and Survivin +/- E/L-selectin, i.v. route, 13 evaluated patients. Comparison of pre-existing and vaccine-induced immune responses in stage IV melanoma patients.

We have efficiently transfected DC with RNA encoding a functional protein (E/L-selectin), which allows entry of DC into LN from HEV. These DC rolled in vitro on sialyl-LewisX-coated slides, and in vivo, mouse E/L-selectin-transfected DC homed to LN after i.v. application. Monocyte-derived and cocktail-matured DC electroporated with a combination of RNAs encoding tumor antigens (MelanA, Mage3, Survivin) and E/L-selectin are currently used in a clinical trial. To increase RNA stability and to obtain a longer-lasting expression of E/L-selectin on DC, thereby providing a higher chance that DC can migraten efficiently to LN, the RNA was modified by introducing different RNA caps, introducing different 3’ UTRs, and by elongation of the poly A tail. Furthermore, mouse experiments have been started in collaboration with P02 to perform quantification of E/L-selectin-transfected DC that migrated into LN by labelling these cells with Indium or SPIO beads.

Immunomonitoring of this trial was based on ELISPOT assays with overlapping peptides covering the whole protein sequence of the tumor antigens MageA3, MelanA and Survivin. Most patients already demonstrated broad responses to numerous peptides prior vaccination. Significantly enhanced responses to several peptides and occurrence of new responses was seen in 6 patients, 5 of which were vaccinated with E/L-S+ DC. These data provide evidence for a superior immunopotency of E/L-selectin expressing DC. The distribution of i.v. given DC is currently being analyzed using Indium labelling.

• molecule type
• ribonucleic acids,
• melanoma antigen MAGE-3,
• selectin,
• survivin,
• Melan A

• organ type
• human lymph node

• cell type
• high endothelial cells,
• Biomaterial

• organism type
• Mus musculus,
• Homo sapiens

• experimental design type
• in vivo design experiment,
• sequential design

• experimental factor type
• Clinical treatment factor

created over 15 years ago (2 March 2009)    last modified over 13 years ago (28 September 2011)   [ RDF ]   [ RelFinder ]