Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer
Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer
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用于雌激素受体（ER）/孕激素受体（PR）双阴性乳腺癌的自体树突状细胞疫苗
DOI：
10.1007/s00262-011-1192-2
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发表时间：
2012-09-01
影响因子：
5.8
通讯作者：
Qian, Ke-Qing
中科院分区：
文献类型：
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作者：
Qi, Chun-Jian;Ning, Yong-Ling;Qian, Ke-Qing
目的大量的临床前信息以及少量的临床信息表明树突状细胞疫苗具有治疗潜力。这项工作的目的是评估接种自体树突状细胞疫苗的 ER/PR 双阴性 II/IIIA 期乳腺癌患者的免疫反应、疾病进展和治疗后生存率。 DC在诱导表面标志物和细胞因子产生的特定因子下成熟。个体皮内免疫四次。测定特异性迟发型 IV 型超敏反应 (DTH)、离体细胞因子产生和淋巴细胞亚群，以评估治疗效果。使用 Kaplan-Meier 曲线分析总生存率和疾病进展率，并与同期未接种 DC 疫苗的患者进行比较。结果没有出现意外或严重的不良反应。 DC疫苗引发Th1细胞因子分泌并增加外周血中NK细胞、CD8+ IFN-γ+细胞，但降低CD3+ T细胞和CD3+ HLA-DR+ T细胞的百分比。大约 58% (18/31) 的患者出现 DTH 阳性反应。使用和未使用 DC 疫苗的患者的总生存率没有差异。 3 年无进展生存期显着延长：76.9% 与 31.0%（使用 DC 疫苗与未使用 DC 疫苗相比，p < 0.05）。结论我们的研究结果强烈表明，肿瘤裂解物脉冲的 DC 提供了标准化且广泛适用的乳腺癌抗原来源，可非常有效地引发抗乳腺癌免疫反应。
PurposeA wealth of preclinical information, as well as a modest amount of clinical information, indicates that dendritic cell vaccines have therapeutic potential. The aim of this work was to assess the immune response, disease progression, and post-treatment survival of ER/PR double-negative stage II/IIIA breast cancer patients vaccinated with autologous dendritic cells pulsed with autologous tumor lysates.MethodsDendritic cell (DC) vaccines were generated from CD14+ precursors pulsed with autologous tumor lysates. DCs were matured with defined factors that induced surface marker and cytokine production. Individuals were immunized intradermally four times. Specific delayed type IV hypersensitivity (DTH) reaction, ex vivo cytokine production, and lymphocyte subsets were determined for the evaluation of the therapeutic efficiency. Overall survival and disease progression rates were analyzed using Kaplan–Meier curves and compared with those of contemporaneous patients who were not administered DC vaccines.ResultsThere were no unanticipated or serious adverse effects. DC vaccines elicited Th1 cytokine secretion and increased NK cells, CD8+ IFN-γ+ cells but decreased the percentage of CD3+ T cells and CD3+ HLA-DR+ T cells in the peripheral blood. Approximately 58% (18/31) of patients had a DTH-positive reaction. There was no difference in overall survival between the patients with and without DC vaccine. The 3-year progression-free survival was significantly prolonged: 76.9% versus 31.0% (with vs. without DC vaccine,p< 0.05).ConclusionOur findings strongly suggest that tumor lysate-pulsed DCs provide a standardized and widely applicable source of breast cancer antigens that are very effective in evoking anti-breast cancer immune responses.