Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma.
MELANOMA RESEARCH(2017)
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 (175mg/m(2)) on day 1 and DCs (2x10(7) 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- 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.
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Key words
carboplatin and paclitaxel chemotherapy,dendritic cell vaccine,HLA-A24,melanoma,WT1
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