Patients with advanced melanoma have a very poor prognosis, with no current effective therapy. The long term objective of the proposed work is to evaluate the efficacy of vaccinating these patients, employing recent advances in the identification of melanoma antigens, new delivery systems for these peptides, a low toxicity systemic adjuvant, and a novel method for evaluating the immune response to the vaccines. Patients enrolled in this phase II trial will receive either of the following peptide-based vaccines: a vaccine comprising synthetic melanoma peptide-pulsed autologous dendritic cells, or a vaccine comprising synthetic melanoma peptides plus granulocyte-macrophage colony-stimulating factor (GM-CSF)-in-adjuvant. Both vaccines will also comprise a tetanus toxoid peptide which stimulates helper T-cell responses in the majority of humans. Vaccine administration will be followed by low-dose IL-2 therapy intended to expand activated T-cells reactive against melanoma peptides.
The specific aims of this work are to assess the immunogenicity and therapeutic efficacy of each treatment as follows: The immunogenicity of each vaccine will be assessed, as measured in vitro by tumor reactive T-cell activity, and in vivo by delayed-type hypersensitivity testing. The immune response in the lymph node draining a vaccination site (this lymph node obtained by sentinel node biopsy following lymph node scintigraphy) will be measured, and compared to the immune response measured in peripheral blood, in order to assess the relative sensitivity of each site for evaluating immune responsiveness to vaccination. The therapeutic efficacy of each vaccine will also be assessed, as measured by tumor burden, and will be correlated with the immunogenicity of each vaccine. This clinical study will determine whether either treatment: (1) will mediate tumor regression in some melanoma patients, (2) will result in increased tumor reactive immune responses as measured in vitro by tumor reactive cytotoxic T cell activity, and in vivo by delayed type hypersensitivity testing. and (3) will stimulate T cell responses directed against immunogens that are more readily evaluable in the draining lymph node than in peripheral blood.
