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: Keitaro Fukuda, Takeru Funakoshi, Toshiharu Sakurai, Yoshio Nakamura, Mariko Mori, Keiji Tanese, Akiko Tanikawa, Junichi Taguchi, Tomonobu Fujita, Masato Okamoto, Masayuki Amagai, Yutaka Kawakami
• Journal: Melanoma research (Melanoma Res) Vol. 27 Issue 4 Pg. 326-334 (08 2017) ISSN: 1473-5636 [Electronic] England
• PMID: 28263240 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Peptide Fragments
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Cancer Vaccines (therapeutic use)
• Carboplatin (pharmacology, therapeutic use)
• Dendritic Cells (immunology)
• Female
• Humans
• Male
• Melanoma (drug therapy, mortality, pathology)
• Middle Aged
• Neoplasm Staging
• Paclitaxel (pharmacology, therapeutic use)
• Peptide Fragments (immunology)
• Pilot Projects
• Skin Neoplasms (drug therapy, mortality, pathology)