This is a Phase I trial in which autologous human dendritic cells (DCs), loaded with control antigens and synthetic tumor-derived peptides, will be used to define safety and toxicity in vivo, and to test for the generation of T cell mediated immunity in patients with melanoma. Patients with AJCC stage III or IV disease will be eligible. Enriched populations of dendritic cells will be generated ex vivo as Langerhans cells (LCs) from CD34+ progenitors, or as monocyte-derived dendritic cells (moDCs) from plastic-adherent, peripheral blood mononuclear cells. These two distinct types of dendritic cells will be compared for safety, toxicity, and vaccination efficacy after in vitro expansion, maturation, and Ag loading, when injected intradermally in vivo. Cohorts of 3-6 patients will be recruited and enrolled alternately in the phase 1a component of the study, to receive vaccinations using only one of two types of dendritic cells, e.g., CD34+ HPC-derived Langerhans cells (LDs) or blood monocyte-derived dendritic cells (moDCs). Dose escalations will occur between groups of patients, rather than within a single patient. Accrual per cohort will be based on dose limiting toxicities or lack thereof. Upon determination of the optimal biologic dose and type of DC in phase 1a, 9 additional patients will be accrued to phase 1b of this trial. Response assessments will be based on changes in T cell function and frequencies measured before and after dendritic cell vaccinations (e.g., cytokine secretion measured in ELISPOT assay, T cell proliferation assay, tetramer frequency, and 51Cr-release CTL assays). DTH reactions to the vaccinations themselves will also be monitored after primary and booster immunizations, with the option to perform skin biopsies. Toxicity of the treatment will be assessed according to standard NCI toxicity criteria. No additional clinical measurements or outcome assessments will be required as part of this research study beyond those that already constitute standard care for patients with this malignancy and stage of disease. We expect to accrue 18-36 patients in phase 1a and 9 patients in phase 1b for a total of 27-45 patients. We expect an accrual rate of approximately 2 patients per month. This study is expected to be completed within 24 months, depending on the toxicity observed in phase 1a.
