Mature Dendritic Cell Immunotherapy Of Metastatic Melanoma- A Phase I Trial

OBJECTIVES:

• Determine the safety and tolerability of antigen-pulsed dendritic cell vaccine in patients with metastatic melanoma.
• Determine the longevity of melanoma-specific immunity in patients treated with this regimen.
• Perform serial analysis of T-cell and B-cell function in patients treated with this regimen.

OUTLINE: Patients receive filgrastim (G-CSF) subcutaneously (SC) once daily on days 1-6 or 1-7. Patients undergo apheresis on days 6 and 7 or 6-8 to obtain peripheral blood mononuclear cells (PBMC). PBMC are processed for CD34+ cell isolation. These autologous CD34+ hematopoietic progenitor cells are cultured to generate dendritic cells (DC). DC are then pulsed with endotoxin-free keyhole limpet hemocyanin and HLA-A2-01 restricted flu-matrix peptides derived from melanoma-associated tumor antigens (MART-1:27-35, gp100:209-217, and MAGE-3). Antigen-pulsed DC are incubated with interferon alfa to induce DC maturation.

Patients receive priming injections of antigen-pulsed DC vaccine SC once every 2 weeks for 8 weeks. Treatment repeats at 2, 3, 4, and 5 months after the last priming injection in the absence of unacceptable toxicity or disease progression.

Patients are followed at 2 and 4 weeks and then every 3 months for 1.5 years.