Patient description: The patient is a 60 year old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is worsening. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions are detected in the head and face. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. His serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). His family history is only significant for hypertension in his mother and DM type 2 in his father. The diagnosis of Paget's Disease of Bone was confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Metastatic Melanoma Patients with histologically proven cutaneous melanoma at one of the following AJCC stages.Regional metastatic disease (any T; N2c or N3; M0). Distant metastatic disease (any T; any N; M1a, M1b or M1c*).*except uncontrolled brain metastasis HLA-A1 or HLA-A2 (by serology or molecular biology) MAGE-3 gene expression by the tumor if patient is HLA-A1 and/or NA17 gene expression by the tumor if patient is HLA-A2 (determined by RT-PCR analysis) Measurable Disease (RECIST v1.1)Patients must have at least 2 cutaneous metastases, suitable for peri-tumoral injection and surgical resection, with their largest diameter equal to or greater than 5 mm Age ≥ 18 years Karnosky Performance status (KPS) ≥70 or WHO performance status of 0 or 1 Expected survival of at least 6 months Normal laboratory values : Platelet count ≥100x103/μL,Leucocyte count ≥ 3x103/μL, Hemoglobin ≥ 9 g/dL, ASAT and ALAT ≤ 2xUNL, Serum creatinine ≤1.5xUNL, Total bilirubin ≤ 1.5xUNL, LDH ≤ 1.5xUNL Viral serology : negative antibodies for HCV & HIV; negative antigens for HBV Patient should agree to perform biopsies and blood collections for translational research  Uncontrolled brain or central nervous system metastases. 2. Previous treatment for the melanoma within 6 weeks from with any reagent known to modulate the immune system such as a cancer vaccine, interferon-alpha, interleukins or anti-CTLA-4 antibodies. 3. Previous chemotherapy, radiotherapy, corticotherapy, or other immune suppressive therapy within 4 weeks from inclusion. 4. Clinically significant cardiovascular disease (including cardiac insufficiency NYHA grade III and IV, unstable angina, arrythmia, myocardial infarction, symptomatic congestive heart failure) in the past 12 months before enrollment. 5. Other serious acute or chronic illnesses, e.g. active infections requiring antibiotics, bleeding disorders or other conditions requiring concurrent medications not allowed during this study. 6. Other malignancy within 3 years prior to entry in the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma. 7. Active immunodeficiency disease or autoimmune disease (Vitiligo is not an criterion). 8. Lack of availability for immunological and clinical follow-up assessments. 9. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. 10. Subject pregnant or breastfeeding, or planning to become pregnant within 6 months after the end of treatment. 11. Subject (male or female) not willing to use highly effective methods of contraception (per institutional standard) during treatment and for 6 months after the end of treatment