Dendritic cell vaccines in metastasized malignant melanoma

Dendritic cells as immunotherapeutic agents against malignancies have been applied for over ten years. Proof of principle studies demonstrated immunogenicity of dendritic cells even in patients suffering from advanced malignancies. Clinicians and immunologists early focused on this innovative immunotherapeutic approach in metastasized malignant melanoma--a malignancy so far resisting most traditional oncologic treatment modalities. In this review we summarize the experience obtained of dendritic cell therapy in patients with malignant melanoma and state past, present and future obstacles. So far over 850 melanoma patients in 51 trials have been reported since 1998. Within these trials there exists a vast heterogeneity concerning type of dendritic cell applied, differentiation and maturation of dendritic cells, type of antigen target and nature, application mode, number of cells applied, vaccination intervals in addition to patients treated at various stages of melanoma. A minority of patients developed anticipated autoimmune adverse events in addition to expected immune system activation symptoms such as fever and local site reaction. As only solitary World Health Organization (WHO) grade III or IV adverse events were reported one can state that dendritic cell therapy is safe. Objective clinical responses have repeatedly been observed in a minority of heavily pretreated and far advanced melanoma patients. Future challenges include optimization and standardization of dendritic cell generation and application, addition of synergistic immunomodulatory agents to enhance immunogenicity and block tumor escape and treatment of patients at earlier stages of disease who will benefit from this innovative therapy.