This study evaluates the safety as well as the potential clinical efficacy of an adoptive transfer of CD8+ T cells, sorted with HLA-peptide multimers and specific for Melan-A and MELOE-1 melanoma antigens, to patients suffering from advanced metastatic melanoma (stages IIIc and IV).

Inclusion Criteria:

• Male or female ≥ 18 and ≤ 75 years

• Patient expressing the HLA-A*0201 subtype of the human leukocyte antigen (HLA -A2)

• Patient with metastatic melanoma stage IIIc or IV (AJCC 2010) except brain metastases

• Tumor expressing the antigens Melan-A and MELOE-1 detected by RT-PCR

• Absence of cerebral metastases

• ECOG ≤ 1 or Karnofsky ≥ 80%

• Prior adjuvant melanoma treatment (before metastatic stage) authorized (anti- BRAF, anti-CTLA4, IFN, TIL... )

• Disease measurable / evaluable within 28 days before the first administration of study treatment

• Negative viral serology (HIV 1/2, Ag p24 , HTLV 1/2 , hepatitis B and C, syphilis)

• Results of analysis:

  • Hemoglobin ≥ 10 g / dl or ≥ 6.25 mmol / l
  • Leukocytes ≥ 4000/μl
  • Lymphocytes ≥ 1500/μl
  • Platelets ≥ 80.000/μl
  • Creatinine ≤ 2.5 N
  • Total bilirubin ≤ 3 N
  • AST and ALT ≤ 3 N without liver metastases; ≤ 5 N with liver metastases

• Negative pregnancy test for women of childbearing age

• Patient affiliated to a social security system

• Patient who has signed informed consent

Exclusion Criteria:

• Brain metastases
• Ocular primitive melanoma
• Treatment of metastatic melanoma by more than two lines (chemotherapy , immunotherapy, targeted therapy or radiotherapy) or within 4 weeks before the inclusion
• Treatment with ipilimumab within 8 weeks before the inclusion
• Known allergy to albumin
• Contraindication to the use of vasopressors
• Positive viral serology for HIV 1/2 , Ag p24 , HTLV 1/2, hepatitis B or C, or syphilis
• Women who are pregnant, nursing or refusing to use contraceptives, women with no negative pregnancy test at baseline
• Presence of a second active cancer (with the exception of cervical cancer in situ or skin cancer other than melanoma)
• History of event or current event of a progressive or non-stabilized severe heart disease (congestive heart failure, coronary artery disease, uncontrolled hypertension, serious arrhythmias or ECG signs of previous myocardial infarction)
• Uncontrolled thyroid dysfunction
• Any serious acute or chronic illness (active infection requiring antibiotics, bleeding disorders or other condition requiring concomitant treatment not allowed in this study)
• History of chronic autoimmune disease (Addison's disease, multiple sclerosis, Graves' disease, rheumatoid arthritis, systemic lupus erythematosus, ... ) with the exception of patients with active vitiligo or a history of vitiligo
• History of uveitis and retinopathy associated with melanoma
• Adults under a legal protection regime (guardianship, trusteeship, "sauvegarde de justice")