Dendritic Cell Based Therapy of Malignant Melanoma

Eligible patients receive vaccination with tumor antigen pulsed autologous monocyte-derived mature dendritic cells with a fixed interval. The dendritic cells are generated from leukapheresis products and frozen after antigen loading.

HLA A2 positive patients are treated with PADRE and oncopeptide pulsed DC; p53, survivin and telomerase peptides. HLA A2 negative patients are treated with KLH and tumorlysate pulsed DC; autologous or allogeneic. Each patient is given 6 immunizations with at least 5x106 peptide/lysate pulsed autologous DC. Vaccination 1-4 is given weekly and 4-6 at 2-week intervals. Those patients who exhibit stable disease, partial response or complete response after 6 injections will be given 4 more vaccinations at 2-week interval. The vaccine is applied by intradermal injection near the inguinal region.

IL-2 2 MIU s.c. day 2-6, Cyclophosphamide (Sendoxan®, Baxter A/S) 50 mg twice a day bi-weekly and 200 mg Celecoxib (Celebra®, Pfizer) daily are used. Scans and re-staging tests are performed at scheduled intervals throughout the study.

Inclusion criteria

• Histologically proven progressive metastatic or locally advanced melanoma
• No standard treatment indicated
• Age: > 18
• WHO-Performance Status 0-1
• At least tone measurable tumor lesions according to the RECIST criteria.
• Life expectancy more than 3 months
• Acceptable CBC and blood chemistry results
• Written informed consent

Exclusion criteria

• Patients with a history of any other neoplastic disease less than 5 years ago (excepting treated carcinomas in situ of the cervix and basal/squamous cell carcinomas of the skin).
• Patients with metastatic disease in the central nervous system (CNS).
• Patients with other significant illness including severe allergy, asthma, angina pectoris or congestive heart failure.
• Patients with acute or chronic infection including HIV, hepatitis and tuberculosis.
• Patients who are pregnant.
• Patients who have received antineoplastic therapy including chemotherapy or immunotherapy less than 4 weeks before beginning the trial.
• Patients who receive corticosteroids or other immunosuppressive agents.
• Baseline serum LDH greater than 2.5 times the upper limit of normal.
• Patients with active autoimmune diseases such as lupus erythematosus, rheumatoid arthritis or thyroiditis.