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.
Division of Immunotherapy, Shizuoka Cancer Center Research Institute,                     Shizuoka 411-8777, Japan.
Chie
C
Oshita
Masako
M
Takikawa
Akiko
A
Kume
Haruo
H
Miyata
Tadashi
T
Ashizawa
Akira
A
Iizuka
Yoshio
Y
Kiyohara
Shusuke
S
Yoshikawa
Ryuji
R
Tanosaki
Naoya
N
Yamazaki
Akifumi
A
Yamamoto
Kazutoh
K
Takesako
Ken
K
Yamaguchi
Yasuto
Y
Akiyama
D000368:Aged; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000097:blood; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D007279:Injections, Subcutaneous; D058965:MART-1 Antigen / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D016019:Survival Analysis; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
D000951:Antigens, Neoplasm; D001323:Autoantibodies; D019496:Cancer Vaccines; D015789:HLA-A2 Antigen; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C420909:Mage-a2 antigen; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin