Immunotherapy of Melanoma Using Dendritic Cells

Summary

Melanoma is a malignant skin tumor of melanocytic origin. No cure is currently available in advanced stages with distant metastasis. Recent progress in the understanding of mechanisms of immune activation and immune escape during an antimelanoma-specific immune response has resulted in new concepts for immunotherapeutic intervention in this disease. In a clinical pilot trial, 30 metastatic melanoma patients were vaccinated with peptide- and/or tumor lysate-pulsed cells. All patients developed a strong delayed-type hypersensitivity (DTH) reaction to the tracer molecule KLH. Peptide-specific immune response could be detected by DTH to peptide-pulsed dendritic cells (DC) and was correlated to response to therapy. DTH reactivity to peptide alone was detected in 6 patients. Clinical responses were induced in 27% (8/30) of the patients including 3 CR (complete remissions) and 5 PR (partial remissions). Immune escape mechanisms were evident at various levels of antigen presentation, including defects in expression of proteasomal antigens, TAP deficiency, melanoma antigen loss variants, and absent expression of relevant HLA surface molecules. DC vaccination for induction of an antitumor response in melanoma patients is safe and promising. However, we believe that aside from the optimal strategy for the induction of an immune response, factors such as a tumor immune escape mechanisms also have to be considered as limitations for therapy.