Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial

Oshita,Chie; Takikawa,Masako; Kume,Akiko; Miyata,Haruo; Ashizawa,Tadashi; Iizuka,Akira; Kiyohara,Yoshio; Yoshikawa,Shusuke; Tanosaki,Ryuji; Yamazaki,Naoya; Yamamoto,Akifumi; Takesako,Kazutoh; Yamaguchi,Ken; Akiyama,Yasuto

doi:10.3892/or.2012.1956

Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial

Authors:
- Chie Oshita
- Masako Takikawa
- Akiko Kume
- Haruo Miyata
- Tadashi Ashizawa
- Akira Iizuka
- Yoshio Kiyohara
- Shusuke Yoshikawa
- Ryuji Tanosaki
- Naoya Yamazaki
- Akifumi Yamamoto
- Kazutoh Takesako
- Ken Yamaguchi
- Yasuto Akiyama
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Affiliations: Division of Immunotherapy, Shizuoka Cancer Center Research Institute, Shizuoka 411-8777, Japan, Department of Dermatology, Shizuoka Cancer Center Hospital, Shizuoka 411-8777, Japan, Division of Pathology and Clinical Laboratory of Medicine, National Cancer Center Hospital, Tokyo 104-0045, Japan, Department of Dermatology, National Cancer Center Hospital, Tokyo 104-0045, Japan, Department of Dermatology, Saitama Medical University, Saitama 350-0495, Japan, Biotechnology Research Laboratories, Takara Bio Inc., Ltd., Shiga 520-2193, Japan
Published online on: August 7, 2012 https://doi.org/10.3892/or.2012.1956
Pages: 1131-1138
Copyright: © Oshita et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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.

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