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.