Durable complete clinical responses in a phase I/II trial using an autologous melanoma cell/dendritic cell vaccine.

摘要: Advanced metastatic melanoma is incurable by standard treatments, but occasionally responds to immunotherapy. Recent trials using dendritic cells (DC) as a cellular adjuvant have concentrated on defined peptides the source of antigens, and rely foreign proteins help generate cell-mediated immune response. This approach limits patient accrual, because currently defined, non-mutated epitopes are restricted small number human leucocyte antigens. It also fails take advantage mutated peculiar patient's own tumour, CD4+ T lymphocytes potential effectors anti-tumour immunity. We therefore sought determine whether fully autologous DC vaccine feasible, therapeutic benefit. Patients with American Joint Cancer Committee stage IV were treated immunotherapy consisting monocyte-derived DC, matured after culture irradiated tumour cells. Of 19 patients enrolled into trial, sufficient was available make treatments for 17. these, 12 received complete priming phase six cycles either 0.9×106 or 5×106 DC/intradermal injection, at 2-weekly intervals. Where possible, treatment continued lower dose 6-weekly The remaining five could not priming, due progressive disease. Three who completed durable responses (average duration 35 months+), three had partial responses, disease (WHO criteria). Disease regression correlated development delayed type hypersensitivity intradermal challenge irradiated, tumour. However, plasma S-100B levels prior commencement objective clinical response (P=0.05) survival (log rank P<0.001). minimal side-effects well tolerated all patients. Mature, preparations exposed appropriate antigen sources can be reliably produced advanced melanoma, in subset those volume their repeated administration results responses.