VACCINATION OF MELANOMA PATIENTS WITH PEPTIDE-PULSED OR TUMOR LYSATE-PULSED DENDRITIC CELLS

Melanoma is the main cause of death in patients with skin cancer(1). C ytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restrict ed and tumor antigen-specific manner. Several melanoma-associated tumo r antigens have been identified(2). These antigens are suitable candid ates for a vaccination therapy of melanoma. Dendritic cells (DCs) are antigen-presenting cells (APCs) specialized for the induction of a pri mary T-cell response(3). Mouse studies have demonstrated the potent ca pacity of DCs to induce antitumor immunity(4-11). In the present clini cal pilot study, DCs were generated in the presence of granulocyte/mac rophage-colony stimulating factor (CM-CSF) and interleukin 4 (IL-4) an d were pulsed with tumor lysate or a cocktail of peptides known to be recognized by CTLs, depending on the patient's HLA haplotype. Keyhole limpet hemocyanin (KLH) was added as a CD4 helper antigen and immunolo gical tracer molecule. Sixteen patients with advanced melanoma were im munized on an outpatient basis. Vaccination was well tolerated. No phy sical sign bf autoimmunity was detected in any of the patients. DC vac cination induced delayed-type hypersensitivity (DTH) reactivity toward KLH in all patients, as well as a positive DTH reaction to peptide-pu lsed DCs in 11 patients. Recruitment of peptide-specific CTLs to the D TH challenge site was also demonstrated. Therefore, antigen-specific i mmunity was induced during DC vaccination. Objective responses were ev ident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (s kin, soft tissue, lung, pancreas) and one additional minor response. T hese data indicate that vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma. Further studies are necessary to demonstrate cli nical effectiveness and impact on the survival of melanoma patients.