Pure autologous tumor cells (TC) and dendritic cells (DC) with GM-CSF: Patient-specific vaccine for metastatic melanoma

Abstract

7547 Background: DC loaded with TC is a promising approach for vaccine therapy. The novel aspect of the product used in this trial is the use of irradiated melanoma TC from autologous cell lines incubated with interferon-gamma (IFN) to enhance expression of HLA and tumor associated antigens. Methods: Pure cultures of melanoma TC are expanded to 108 cells, incubated with 103 U/ml IFN for 72 hrs, irradiated, then cryopreserved. DC are generated from peripheral blood by incubating mononuclear cells in AIM V medium with 1000 U/ml GM-CSF and 1000 U/ml IL-4 for one week. DC and TC are co-incubated overnight, then cryopreserved in aliquots of about 107 cells. For treatment, vial contents are suspended in 500 mg GM-CSF for each s.c. injection. After a baseline delayed-type hypersensitivity (DTH) test to an i.d. injection of 106 irradiated TC at week-0, patients receive s.c. vaccinations weekly × 3, then monthly × 5. The DTH test to autologous TC is repeated at week-4. Results: Cell lines have been established for 75% of patients and vaccines prepared from 60% of the lines. As of 12/01/03, 21 patients had been entered. 16 had received prior i.v. IL-2 and/or chemotherapy; 7 had measurable disease at entry. 138 vaccine injections have been administered; 16 patients have completed the entire series. At the median follow-up of 8 mos, progression-free survival is 51%. All 21 patients were still alive with the longest followed more than 2.5 years since starting the vaccine. The only common adverse event is mild erythema at the injection site. One patient had an anaphylactoid reaction following her 8th and final injection. No patients were anergic at baseline, but all were DTH-. 8/21 (38%) subsequently exhibited an immune response to autologous tumor; 5 became DTH+ at 4 weeks and 3 more at 6 mos. Conclusions: This patient-specific DC/autologous TC vaccine is feasible and well tolerated. The DTH conversion rate is encouraging, as are the progression-free and overall survival rates. No significant financial relationships to disclose.