Inclusion Criteria:

• Histologically confirmed melanoma that is considered surgically incurable with either:

  • Stage IIIc melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis.
  • Stage IV melanoma (M1a, M1b or M1c).
• At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site.
• MART-1 positive melanoma by RT-PCR or IHC.
• HLA-A*0201 (HLA-A2.1) positivity by molecular subtyping.
• Age greater than or equal to 18 years old.
• Life expectancy greater than 3 months assessed by a study physician.

• A minimum of one measurable lesion defined as:

  • Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST).
  • Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s).
• No restriction based on prior treatments.
• ECOG performance status (PS) 0 or 1.

• Adequate bone marrow and hepatic function determined within 30-60 days prior to enrollment, defined as:

  • Absolute neutrophil count more than 1.5 x 109 cells/L.
  • Platelets more than 100 x 109/L.
  • Hemoglobin more than 10 g/dL.
  • Aspartate and alanine aminotransferases (AST, ALT) less than 2.5 x ULN (less than 5 x ULN, if documented liver metastases are present).
  • Total bilirubin less than 2 x ULN (except patients with documented Gilbert's syndrome).
  • Creatinine less than 2 mg/dl (or a glomerular filtration rate greater than 60).
• Must be willing and able to accept at least two tumor biopsies.
• Must be willing and able to accept at least two leukapheresis procedures.
• Must be willing and able to provide written informed consent.

Exclusion Criteria:

• Previously known hypersensitivity to any of the agents used in this study.
• Received systemic treatment for cancer, including immunotherapy, within one month prior to dosing.
• Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed).
• HIV seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist.
• Hepatitis B or C seropositivity, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist.
• Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
• Clinically active brain metastases. Radiological documentation of absence of active brain metastases at screening is required for all patients.
• Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 14 days from starting the conditioning chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators.

• Since IL-2 is administered following cell infusion:

  • Patients will be excluded if they have a history of clinically significant EKG abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test)
  • Similarly, patients who are 50 years old with a baseline LVEF < 45% will be excluded.
  • Patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction who do not have a normal pulmonary function test as evidenced by a FEV1 < 60% predicted will be excluded.