Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma

Keitaro Fukuda, Takeru Funakoshi, Toshiharu Sakurai, Yoshio Nakamura, Mariko Mori, Keiji Tanese, Akiko Tanikawa, Junichi Taguchi, Tomonobu Fujita, Masato Okamoto, Masayuki Amagai, Yutaka Kawakami

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

In this study, we aimed to evaluate the feasibility and efficacy of peptide-pulsed dendritic cell (DC) vaccine in combination with carboplatin and paclitaxel chemotherapy (DCCP) for patients with stage IV melanoma previously treated with dacarbazine-containing regimen. Six HLA-A24 and 3 HLA-A02 patients were treated with carboplatin (area under the curve 5) and paclitaxel (175 mg/m) on day 1 and DCs (2×10 cells) pulsed with Wilms tumor gene 1 (WT1), gp100, tyrosinase, and either MAGE-A3 (for HLA-A24) or MAGE-A2 (for HLA-A02) peptides on days 8 and 22 in 28-day cycle for up to three cycles. DCCP was well tolerated, and median progression-free survival and median overall survival were 2.3 and 12.0 months, respectively. In four of nine patients, a WT1-specific immune response (WT1-IR) was detected using the interferon-γ enzyme-linked ImmunoSpot assay and WT1/HLA tetramer assay. DCCP was more likely to elicit a WT1-IR in patients who received DCs pulsed with the HLA-A24-restricted peptide (75%) compared with patients who received DCs pulsed with the HLA-A02-restricted peptide (0%, P=0.058). Furthermore, three (75%) of four patients with a WT1-IR survived longer than 12 months, whereas only one (20%) of five patients without a WT1-IR who received the BRAF inhibitor after DCCP survived longer than 12 months. These results suggest that DCCP may be beneficial for HLA-A24 melanoma patients with a WT1-IR.

Original languageEnglish
JournalMelanoma Research
DOIs
Publication statusAccepted/In press - 2017 Mar 3

Fingerprint

Combined Vaccines
Wilms' Tumor Genes
Carboplatin
Wilms Tumor
Paclitaxel
Dendritic Cells
Melanoma
HLA-A24 Antigen
Drug Therapy
Peptides
varespladib methyl
HLA-A2 Antigen
Enzyme-Linked Immunospot Assay
Dacarbazine
Monophenol Monooxygenase
Interferons
Disease-Free Survival
Area Under Curve
Survival

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

Cite this

Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma. / Fukuda, Keitaro; Funakoshi, Takeru; Sakurai, Toshiharu; Nakamura, Yoshio; Mori, Mariko; Tanese, Keiji; Tanikawa, Akiko; Taguchi, Junichi; Fujita, Tomonobu; Okamoto, Masato; Amagai, Masayuki; Kawakami, Yutaka.

In: Melanoma Research, 03.03.2017.

Research output: Contribution to journalArticle

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AU - Tanese, Keiji

AU - Tanikawa, Akiko

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