OBJECTIVES:

• Determine the safety and adverse event profile of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody combined with tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 in patients with resected stage III or IV melanoma.
• Determine if this regimen causes antigen-specific T-cell activation in these patients.
• Determine the clearance profile of this regimen in these patients.
• Assess the development of host immune response in patients treated with this regimen.

OUTLINE: This is a dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-CTLA4).

Patients receive tyrosinase:368-376, gp100:209-217, and MART-1:26-35 peptides emulsified in Montanide ISA-51 subcutaneously followed by MDX-CTLA4 IV over 90 minutes at 0, 1, 2, 3, 4, 5, 8, and 11 months in the absence of disease progression or unacceptable toxicity.

Cohorts of at least 6 patients receive escalating doses of MDX-CTLA4 until the maximum tolerated dose is determined.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter until disease progression.

PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed completely resected stage III or IV melanoma

  • Mucosal or ocular subtypes allowed
• HLA-A2 positive
• Positive staining of tumor tissue with antibody HMB-45 for gp100, tyrosinase, and/or MART-1
• Failed (or ineligible for or refusal of) interferon alfa

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Karnofsky 60-100%

Life expectancy:

• At least 12 months

Hematopoietic:

• WBC at least 2,500/mm^3
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10 g/dL
• Hematocrit at least 30%

Hepatic:

• Bilirubin no greater than upper limit of normal (ULN)
• AST no greater than 1.25 times ULN
• Hepatitis B surface antigen negative
• Hepatitis C antibody nonreactive

Renal:

• Creatinine less than 1.25 times ULN

Immunologic:

• Antinuclear antibody (ANA) negative OR

• If ANA positive, must be:

  • Antithyroglobulin antibody negative
  • Rheumatoid factor negative
  • Anti-LKM antibody negative
  • Anti-phospholipid antibody negative
  • Anti-islet cell antibody negative
  • Anti-neutrophil cytoplasmic antibody negative
• HIV negative
• No autoimmune disease (e.g., uveitis or autoimmune inflammatory eye disease)
• No active infection
• No hypersensitivity to tyrosinase:368-376, gp100:209-217, MART-1:26-35, or Montanide ISA-51

Other:

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
• No underlying medical condition that would preclude study
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
• No prior tyrosinase, gp100, or MART-1 peptide
• No prior antitumor vaccination
• No prior interleukin-2
• At least 4 weeks since prior immunotherapy for melanoma

Chemotherapy:

• At least 4 weeks since prior chemotherapy for melanoma

Endocrine therapy:

• At least 4 weeks since prior hormonal therapy for melanoma
• At least 4 weeks since prior corticosteroids
• No concurrent systemic or topical corticosteroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy for melanoma

Surgery:

• See Disease Characteristics

Other:

• No prior cytotoxic therapy
• At least 4 weeks since any other prior therapy for melanoma
• Concurrent analgesics allowed if on stable dose for at least 2 weeks before study