mRNA Electroporated Autologous Dendritic Cells for Stage III/IV Melanoma

Inclusion Criteria: 1. Able and willing to give written informed consent 2. Histological documentation of AJCC stage III or stage IV melanoma 3. melanoma (melanoma originating in the choroid, iris or ciliar body are not eligible) 4. baseline tumor assessment by whole-body FDG-PET/CT, patients should be free from measurable tumor lesions (RECIST (v1.1)), and free from symptomatic non-measurable tumor lesions 5. Prior local treatment of primary and metastatic tumor lesions is allowed . Treated tumor lesions should be free from progression at baseline assessment 6. Normal organ function and normal hematological parameters;laboratory parameters should be within normal range, except following laboratory parameters:HEMOGLOBIN ≥ 10 G/DL; GRANULOCYTES ≥ 1,500/µL; LYMPHOCYTES ≥ 1000/µL; PLATELETS ≥ 100,000/µL; SERUM CREATININ ≤ 2.0 MG/DL; SERUM BILIRUBIN ≤ 2.0 MG/DL; AST AND ALT ≤ 2 X THE NORMAL UPPER LIMITS; LDH ≤ 1,5X NORMAL UPPER LIMIT; CRP ≤ 1,5X NORMAL UPPER LIMIT; PROTHROMBIN TIME (PT) INTERNATIONAL NORMALIZED RATIO (INR) AND PARTIAL THROMBOPLASTIN TIME (PTT) WITHIN NORMAL LIMITS 7. Negative serology for HCV, and HIV; absence of active infection with HBV, and Syphilis; If positive results for HepB or Syphilis indicate immunity and are not indicative of active infection, the patient can enter the study. 8. Adequate venous access(to undergo leukapheresis) 9. No prior systemic therapy for melanoma 10. Full recovery from all prior therapies. A period of 4 weeks following major surgery, radiation therapy, or ILP, or any other major invasive procedure is required 11. Baseline WHO performance status of 0 or 1 12. Male and female patients ≥ 18 years 13. No need for uninterrupted therapeutic anticoagulation 14. No prior history of a serious autoimmune disorder 15. No concomitant medication with immune suppressive drugs 16. Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Exclusion Criteria: 1. Evidence of immunodeficiency or autoimmune disease requiring medical treatment (e.g. corticosteroids or other immunosuppressive drugs).Vitiligo is not an exclusion criterion 2. Any serious acute or chronic illnesses (e.g. heart disease NYHA Class III or IV,renal-,liver- or pulmonary insufficiency) or other conditions requiring concurrent medications not allowed during this study (e.g. active chronic infections requiring antibiotics) 3. History of malignancy. Curatively treated cervical carcinoma in situ,or squamous-,or basal cell carcinoma of the skin, or subjects who have been treated and recurrence-free of other malignancies for more than 5 years following the diagnosis are eligible 4. Inability to undergo FDG-PET/CT, or MRI examination 5. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study 6. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment 7. Subject is pregnant (positive serum beta-HCG test at screening) or is currently breast-feeding, anticipates becoming pregnant/impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment 8. Current alcohol dependence or drug abuse 9. Known hypersensitivity to the study treatment 10. Legal incapacity or limited legal capacity 11. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. 12. Signs and symptoms suggestive of transmissible spongiform encephalopathy,or family members who suffer(ed) from such.