title: Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma.
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.
authors.affiliation: aDepartment of Dermatology bDivision of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine cTokyo Midtown Clinic, Tokyo, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Fukuda
authors.forename: Takeru
authors.initials: T
authors.lastname: Funakoshi
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mariko
authors.initials: M
authors.lastname: Mori
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanese
authors.forename: Akiko
authors.initials: A
authors.lastname: Tanikawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Taguchi
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Fujita
authors.forename: Masato
authors.initials: M
authors.lastname: Okamoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000368:Aged; D019496:Cancer Vaccines / Q000627:therapeutic use*; D016190:Carboplatin / Q000494:pharmacology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000276:immunology*; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D019496:Cancer Vaccines; D010446:Peptide Fragments; D016190:Carboplatin; D017239:Paclitaxel