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")
