Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

RATIONALE: Vaccines made from a person's dendritic cells mixed with tumor peptides and proteins may help the body build an effective immune response to kill tumor cells. Infusing the vaccine directly into the lymphatic system may cause a stronger immune response and kill more tumor cells. PURPOSE: This randomized phase I trial is studying the side effects and best dose of two dendritic cell vaccines in treating patients with stage III or stage IV melanoma.

OBJECTIVES: Primary * Compare the safety of intralymphatic autologous type-1-polarized dendritic cell vaccine vs autologous mature dendritic cell vaccine loaded with antigenic peptides and proteins in patients with stage III or IV melanoma. Secondary * Determine peripheral blood CD8+ and CD4+ T-cell responses to HLA-presented melanoma epitopes and autologous tumor cells using interferon gamma and interleukin-5 ELISPOT assay. * Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients. * Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients. * Correlate treatment-associated changes in immune response with clinical outcome. OUTLINE: This is a randomized, open-label, dose-escalation study. Patients are randomized to 1 of 2 formulations of dendritic cell (DC) vaccines. * Arm I: Patients receive intralymphatic autologous type-1-polarized (by interleukin-1-beta, tumor necrosis factor \[TNF\] alfa, interferon alfa, poly-I:C, and interferon gamma) DC vaccine that has been loaded with tumor-related peptide antigens (gp100:209-217\[210M\] peptide, tyrosinase peptide, MART-1:27-35 peptide, MAGE-3/6, and EphA2) and proteins (keyhole limpet hemocyanin \[KLH; first course\] or pan-DR epitope \[PADRE\] \[second course\]) every 6 hours on days 1-4 of weeks 1 and 6. * Arm II: Patients receive intralymphatic autologous mature (by interleukin-1-beta, TNF alfa, interleukin-6, and prostaglandin E\_2) DC vaccine that has been loaded with tumor-related peptide antigens and proteins as in arm I every 6 hours on days 1-4 of weeks 1 and 6. Patients achieving complete response receive 2 more courses of treatment (3 months apart). Patients achieving partial response receive up to 10 more courses of treatment (1 month apart) in the absence of disease progression or unacceptable toxicity. In each arm, cohorts of 4-7 patients receive escalating doses of DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 7 patients experience dose-limiting toxicity. Blood samples are obtained at baseline and periodically during and after treatment. Samples are examined by immunoenzyme techniques for immunologic measurements. After completion of study therapy, patients are followed periodically for 10½ years and then annually thereafter. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.