A comparison of two types of dendritic cell as adjuvants for the inductionof melanoma-specific T-cell responses in humans following intranodal injection

Dendritic cells (DCs) elicit potent anti-tumoral T-cell responses in vitro and in vivo. However, different types of DC have yet to be compared for the ir capacity to induce antitumor responses in vivo at different developmenta l stages. Herein, we correlated the efficiencies of different types of mono cyte-derived DC as vaccines on the resulting anti-tumor immune responses in vivo. Immature and mature DCs were separately pulsed with a peptide derive d from tyrosinase, MelanA/MART-1 or MAGE-1 and a recall antigen. Both DC po pulations were injected every 2 weeks in different lymph nodes of the same patient. Immune responses were monitored before, during and after vaccinati on. Mature DCs induced increased recall antigen-specific CD4(+) T-cell resp onses In 7/8 patients, while immature DCs did so in only 3/8, Expansion of peptide-specific IFN-gamma -producing CD8(+) T cells was observed in 5/7 pa tients vaccinated with mature DCs but in only 1/7 using immature DCs, Howev er, these functional data did not correlate with the tetramer staining. Her ein, immature DCs also showed expansion of peptide-specific T cells. In 2/4 patients vaccinated with mature DCs, we observed induction of peptide-spec ific cytotoxic T cells, as monitored by chromium-release assays, whereas im mature DCs failed to induce peptide-specific cytotoxic T cells in the same patients. Instead, FCS-cultured immature DCs induced FCS-specific IgE respo nses in patient. Our data demonstrate that this novel vaccination protocol is an efficient approach to compare different immunization strategies withi n the same patient. Thus, our data define FCS-free cultured mature DCs as s uperior inducers of T-cell responses in melanoma patients. (C) 2001 Wilcy-L iss, Inc.