• Anti-tumor immune response as assessed by ELISPOT assays, tetramer assays for T cell activity in peripheral blood mononuclear cells, and delayed type hypersensitivity skin test at 3 and 6 months [ Designated as safety issue: No ]
  
• Safety and toxicity immediate and long-term [ Designated as safety issue: Yes ]
  

• Tumor response rate and time to tumor progression by RECIST criteria at 3, 6, 9, and 12 months [ Designated as safety issue: No ]
  
• Disease-free and overall survival at 3, 6, 9, and 12 months [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the specific anti-tumor immune response in patients with stage IIIC or IV malignant melanoma treated with vaccine therapy comprising autologous tumor cells and a sargramostim (GM-CSF)-producing and CD40L-expressing cell line (GM.CD40L).
• Determine the toxicity of this regimen in these patients.

Secondary

• Determine the tumor response rate, time to progression, disease-free survival, and overall survival of patients treated with this regimen.
• Determine the specific anti-tumor immune response and anti-tumor immune response rate in HLA -A2-positive patients treated with this regimen.

OUTLINE: Patients undergo surgical resection of malignant lymph nodes or systemic metastases (isolated metastases or symptomatic lesions) for collection of autologous tumor cells for vaccine production. Vaccine is formulated by combining equal volumes of irradiated autologous tumor cells and irradiated cells from a cell line producing sargramostim (GM-CSF) and expressing CD40L (GM.CD40L).

Patients receive vaccine comprising autologous tumor cells and GM.CD40L intradermally on day 1. Treatment repeats every 28 days for 3 courses. Patients with stable or responding disease at 3 months receive 3 additional courses of booster vaccine. Patients with no evidence of disease progression at 12 months receive 3 more courses of booster vaccine. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 20-50 patients will be accrued for this study within 20 months.