The main objective of this study is to evaluate the clinical and biologic toxicity of cell therapy by adoptive transfer of TIL in combination with intra-tumoral injections of Ad-INFg.

Pre-Inclusion Criteria:

• Male or female patients ≥ 18 and ≤ 75 years of age
• Patients must have signed informed consent
• A negative pregnancy test for women with childbearing potential
• Patients with stage IIIc/IV metastatic melanoma (AJCC 6th edition) with nodal relapse, in transit metastasis, unresectable cutaneous metastases, visceral metastases except bone and brain metastases
• Presence of at least one lesion accessible for intra-tumoral injections of Ad-IFNg
• A negative brain scan, eliminating any brain metastases
• ECOG performance status of 0-2
• Adequate bone-marrow reserve, renal function and hepatic function as assessed by standard laboratory criteria
• Subjects affiliated to an appropriate social security system

Inclusion Criteria:

• Negative viral serology (HIV ½, p24 Ag, HTLV 1 / 2, B and C hepatitis)

Exclusion Criteria:

• For female : the patient is pregnant or lactating or not using contraception and proved by a negative pregnancy test
• Positive viral serology for HIV ½, p24 Ag, HTLV 1 / 2 or B and C hepatitis
• History or current manifestations of severe progressive heart disease (congestive heart failure, coronary artery disease, uncontrolled arterial hypertension, serious rhythm disorders or ECG signs of previous myocardial infarction)
• Any serious illness, acute or chronic, e.g. active infection requiring antibiotics, bleeding disorders or any other condition that requires concomitant medications not allowed during this study
• Presence of a second active cancer except in situ cervical cancer or skin carcinoma
• Intercurrent disease requiring a corticosteroid treatment or a treatment with interferon-α
• Any autoimmune disease including active diabetes mellitus or immunodeficiency. Vitiligo in not an exclusion criteria
• Uncontrolled thyroid dysfunction
• Concurrently participation in a biomedical research (drug or radiotherapy) within the month preceding inclusion
• Metastatic lymph node stage alone with an indication of lymphadenectomy
• Brain or bone metastases discovered by radiological examination during the inclusion assessment
• Surgically resectable metastases
• Ocular melanoma
• More than one line of chemotherapy for treatment of melanoma
• Chemotherapy, immunotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-ureas and mitomycin C)
• Contraindication for the use of vasopressor agents
• Treatment with molecules in pre-marketing development or whose development is finished less than 4 weeks