RATIONALE: Cytotoxic T lymphocytes (CTL) are cells of the immune system that can fight infections and cancer. These CTL can be manipulated in the laboratory so that they can target an individual's cancer.

PURPOSE: This early phase trial is studying the feasibility and side effects of intravenous infusions of CTL generated in the laboratory. To produce the CTL, the study participant's own immune cells are collected by a procedure called a leukapheresis. The cells then undergo laboratory processing for three weeks. Part of this processing includes mixing the patients immune cells with a new kind of cell that has some extra genes added to it. These extra genes are to "teach" the participant's own immune cells to become anti-tumor CTL that can attack the melanoma.

DETAILED OUTLINE: This is an early phase pilot/feasibility trial.

Study subjects will be sequentially accrued to three cohorts. Cohorts 1 and 2 will evaluate the safety and feasibility of infusing two different doses of CTL.

• Participants in all cohorts will undergo two CTL infusions 5 weeks apart.
• Procedures performed during the trial will include physical examinations, laboratory tests, delayed hypersensitivity testing, and skin biopsies.
• Between 5 and 8 days after the first CTL infusion, a biopsy or excision of a melanoma lesion may be performed.
• Three leukapheresis procedures will be performed: two to collect peripheral blood for CTL production and one for research purposes at the end of the clinical trial.
• Radiology tests (including CT scans) will be performed prior to infusion and about 4-5 weeks after the second CTL infusion.

Inclusion Criteria:

• Patients with metastatic melanoma: Either unresectable Stage III or any Stage IV
• ECOG of 0 or 1
• HLA-A*0201 haplotype
• Baseline tumor biopsy MART1/Melan-A expression present (in >10% of tumor cells)
• Patient provides consent for all required biopsies
• Adequate intravenous access for leukapheresis
• Absolute lymphocyte count >500/ul at least once within 30 days of leukapheresis
• Life expectancy greater than 4 months in the opinion of the study clinician
• Negative pregnancy test

Exclusion Criteria:

• Administration of systemic corticosteroids within 28 days of planned leukapheresis
• Administration of cytotoxic chemotherapy or anti-tumor immunotherapy within 28 days of planned leukapheresis
• Administration of radiotherapy within 28 days of planned leukapheresis with the exception of subjects accrued to Cohort 3
• Active autoimmunity requiring systemic immunosuppressive therapy
• HIV infection
• Previous enrollment on this protocol and infusion of MART1/Melan-A CTL