Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial
Metastatic and chemoresistant melanoma can be a good target of immunotherapy             because it is an intractable cancer with a very poor prognosis. Previously, we             tested a dendritic cell (DC)-based phase I vaccine, and confirmed that it was             safe. In the present study, we performed a phase II trial of a DC vaccine for             metastatic melanoma patients with mainly the HLA-A24 genotype, and investigated             the efficacy of the vaccine. Twenty-four patients with metastatic melanoma were             enrolled into a phase II study of DC-based immunotherapy. The group included 19             HLA-A24-positive (A*2402) patients and 3 HLA-A2-positive (A*0201) patients. The             protocol for DC production was similar to that in the phase I trial. Briefly,             a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-A2,             MAGE-A3 and MART-1 or MAGE‑A1) restricted to HLA-A2 or A24 and KLH were used for             DC pulsing. Finally, DCs were injected subcutaneously (s.c.) into the inguinal             region in the dose range of 1-5x107 per shot. The DC ratio (lin-HLA-DR+) of the             vaccine was 38.1±13.3% and the frequency of CD83+ DCs was 25.7±20.8%. Other parameters             regarding DC processing were not different from phase I. Immune response-related             parameters including the ELISPOT assay, DTH reaction to peptide or KLH, DC injection             numbers were shown to be related to a good prognosis. The ELISPOT reaction was             positive in 75% of the patients vaccinated. The increase of anti-melanoma antigen             antibody titer before vaccination was also shown to be a prognosis factor, but             that post-vaccination was not. Based on immunohistochemical analysis, CD8 and             IL-17 were not involved in the prognosis. Adverse effects of more than grade III             were not seen. Overall survival analysis revealed a significant survival prolongation             effect in DC-given melanoma patients. These results suggest that peptide cocktail-treated             DC vaccines may be a safe and effective therapy against metastatic melanoma in             terms of prolongation of overall survival time.