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

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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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 1-5×107 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.

Original languageEnglish
Pages (from-to)1131-1138
Number of pages8
JournalOncology reports
Volume28
Issue number4
DOIs
Publication statusPublished - 2012 Oct 1
Externally publishedYes

Keywords

  • Dendritic cell
  • HLA-A24
  • Immunotherapy
  • Metastatic melanoma
  • Overall survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Oshita, C., Takikawa, M., Kume, A., Miyata, H., Ashizawa, T., Iizuka, A., Kiyohara, Y., Yoshikawa, S., Tanosaki, R., Yamazaki, N., Yamamoto, A., Takesako, K., Yamaguchi, K., & Akiyama, Y. (2012). Dendritic cell-based vaccination in metastatic melanoma patients: Phase II clinical trial. Oncology reports, 28(4), 1131-1138. https://doi.org/10.3892/or.2012.1956