High-Dose Interleukin-2 (HDIL-2), Combined With recMAGE-A3 + AS15 ASCI

Inclusion Criteria:

1. STEP 1 Written informed consent has been obtained from the patient before the performance of any protocol-specific procedure.
2. Male or female patient with histologically proven, measurable unresectable or metastatic cutaneous melanoma
3. Patient is \>/= 18 years of age.
4. Formalin-fixed paraffin-embedded (FFPE) tumor tissue must be available for MAGE-A3 expression screening test from cutaneous, subcutaneous, lymph node lesion, lung or liver lesion. Archival FFPE tumor tissue can be provided for the MAGE-A3 screening test, as long as the FFPE tumor tissue was obtained from a biopsy or resection and no systemic chemotherapy, immunotherapy or targeted therapy has been received by the patient between the tumor collection and the MAGE-A3 screening test. Fresh tumor tissue in RNAlater must be also available for gene signature testing. Patients must have at least one biopsiable cutaneous, subcutaneous, lymph node lesion, The tumor sample should be preferably from the same lesion as the FFPE tumor tissue. Cutaneous lesions must measure \>/= 4mm and lymph nodes, subcutaneous, lung or liver lesions must measure \>/= 1cm.
5. STEP 2 ANA (antinuclear antibody) titer \< 1:80
6. STEP 2 The patient's tumor shows expression of MAGE-A3 gene.
7. ECOG performance status of 0 or 1.
8. WBC \>/= 3000/mm\^3 and Hemoglobin \>/= 9 g/dl
9. Platelet count \>/= 100,000/mm\^3.
10. Normal AST and ALT except for patients with liver metastases, in which serum ALT and AST \</= 2.5 X upper limit of normal (ULN) will be permitted.
11. Creatinine \</= 1.5 mg/dL
12. Normal total bilirubin except for patients with liver metastases, in which total bilirubin \</= 1.5 X ULN will be permitted (patients with Gilbert's syndrome must have a total bilirubin less that 3.0 mg/dL).
13. LDH \</= 2 X ULN
14. Stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test that will rule out cardiac ischemia) with estimated ejection fraction \>50% within 6 months of signing consent form
15. Pulmonary function tests showing FEV1 \> 65% or FVC \> 65% of predicted within 6 months of signing consent form
16. Women of childbearing potential (WOCBP) must be using an adequate method of contraception prior to treatment, throughout the study, and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as: Amenorrhea for 12 consecutive months without another cause, or For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level 35 mIU/mL.
17. (Continued #16) Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days before the start of treatment.
18. Men must also agree to use an adequate method of contraception.

Exclusion Criteria:

1. The patient has at any time received systemic chemotherapy, immunotherapy or targeted therapy (except for isolated limb perfusion, interferon, or radiation in the adjuvant setting, as long as this was performed at least 4 weeks before first study treatment administration).
2. Brain metastasis or history of brain metastasis.
3. Any types of melanoma other than cutaneous, i.e. ocular or mucosal .
4. The patient received any cancer immunotherapeutic containing a MAGE-A3 antigen.
5. Patients with a history of second malignancies are eligible provided that they have been free of recurrence from secondary malignancy for at least 3 years, does not include squamous cell carcinoma, basal cell carcinoma, or carcinoma in situ.
6. The patient has a history of an autoimmune disease such as, but not limited to, multiple sclerosis, lupus, rheumatoid arthritis, and inflammatory bowel disease or an antinuclear antibody (ANA) titer \> 1:80.
7. The patient has a history of allergic disease or reactions likely to be exacerbated by any component of the study investigational compound.
8. The patient has a family history of congenital or hereditary immunodeficiency.
9. Known to be positive for viral hepatitis B or C (HBsAg or Anti HCV) or HIV (HIV antibodies) Patients should have a negative test within 6 months of starting treatment.
10. Systemic steroid therapy, steroid-containing compounds or any other immunosuppressive agents or to be used for more than 7 consecutive days (at a dose of prednisone or equivalent of \>/= 0.125 mg/kg/day).
11. The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with the trial procedures. Each patient will be evaluated by the principal investigator or his designee.
12. The patient has concurrent severe medical problems, unrelated to the malignancy, that would significantly limit full compliance with the study or expose the patient to unacceptable risk. Each patient will be evaluated by the principal investigator or his designee.
13. Initiation of another anti-cancer therapy.
14. For female patients: the patient is pregnant or lactating.
15. WOCBP who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy.