Adoptive Transfer of Specific Melanoma Antigens CD8+ T Cells in Metastatic Melanoma Patients: a Phase I/II Study

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")