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

Abstract

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 their capacity to induce anti‐tumor responses in vivo at different developmental stages. Herein, we correlated the efficiencies of different types of monocyte‐derived DC as vaccines on the resulting anti‐tumor immune responses in vivo. Immature and mature DCs were separately pulsed with a peptide derived from tyrosinase, MelanA/MART‐1 or MAGE‐1 and a recall antigen. Both DC populations were injected every 2 weeks in different lymph nodes of the same patient. Immune responses were monitored before, during and after vaccination. Mature DCs induced increased recall antigen‐specific CD4⁺ T‐cell responses in 7/8 patients, while immature DCs did so in only 3/8. Expansion of peptide‐specific IFN‐γ–producing CD8⁺ T cells was observed in 5/7 patients vaccinated with mature DCs but in only 1/7 using immature DCs. However, these functional data did not correlate with the tetramer staining. Herein, immature DCs also showed expansion of peptide‐specific T cells. In 2/4 patients vaccinated with mature DCs, we observed induction of peptide‐specific cytotoxic T cells, as monitored by chromium‐release assays, whereas immature DCs failed to induce peptide‐specific cytotoxic T cells in the same patients. Instead, FCS‐cultured immature DCs induced FCS‐specific IgE responses in 1 patient. Our data demonstrate that this novel vaccination protocol is an efficient approach to compare different immunization strategies within the same patient. Thus, our data define FCS‐free cultured mature DCs as superior inducers of T‐cell responses in melanoma patients.