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自体独特型致敏树突状细胞瘤苗免疫治疗期Ⅰ多发性骨髓瘤患者的细胞免疫应答

Induction of cellular immune responses in patients with stage-I multiple myeloma after vaccination with autologous idiotype-pulsed dendritic cells.

机构信息

Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Germany.

出版信息

J Immunother. 2011 Jan;34(1):100-6. doi: 10.1097/CJI.0b013e3181facf48.

Abstract

Idiotype vaccines have shown both biological efficacy and clinical benefit in lymphoma. Circulating idiotype proteins (Id) in multiple myeloma patients offer a suitable target for immunotherapy. So far, specific immune responses after vaccination with Ids have been evaluated mostly in advanced myeloma. We explored the potential of dendritic-cell (DC)-based immunotherapy in 9 patients with stage-I disease. Mature monocyte-derived Id-pulsed DCs and keyhole limpet hemocyanin (KLH) were administered at dose levels between 2 and 20×10⁶ cells. Patients received 5 immunizations every 4 weeks. A median number of 6.8×10⁶ DCs were administered per vaccination. Five out of 9 patients (56%) developed Id-specific T cells as showed in proliferation assays and 8 out of 9 patients (89%) showed specific T-cell-mediated cytokine release after Id stimulation. The cytokine-secretion did not show a distinct Th1-type or Th2-type pattern. The M protein dropped slightly in 3 out of 9 patients. We could show that DC-based Id vaccination is a feasible way of inducing specific T-cell responses in stage-I myeloma patients. Further trials are needed to increase the rate of responses and to define the role of DC-based vaccination in the era of new pharmacologic therapies.

摘要

独特型疫苗在淋巴瘤中显示出了生物学疗效和临床获益。多发性骨髓瘤患者的循环独特型蛋白 (Id) 为免疫治疗提供了一个合适的靶标。到目前为止,对用 Id 进行疫苗接种后的特异性免疫反应的评估主要集中在晚期骨髓瘤中。我们在 9 名 I 期疾病患者中探索了树突状细胞 (DC) 为基础的免疫疗法的潜力。在 2 至 20×10⁶ 个细胞剂量水平下给予成熟的单核细胞来源的 Id 脉冲 DC 和血蓝蛋白 (KLH)。患者每 4 周接受 5 次免疫接种。每次接种给予中位数为 6.8×10⁶ 的 DC。9 名患者中有 5 名(56%)在增殖试验中产生了独特型特异性 T 细胞,9 名患者中有 8 名(89%)在 Id 刺激后显示出特异性 T 细胞介导的细胞因子释放。细胞因子释放没有表现出明显的 Th1 型或 Th2 型模式。3 名患者中的 M 蛋白略有下降。我们能够证明基于 DC 的独特型疫苗接种是诱导 I 期骨髓瘤患者特异性 T 细胞反应的一种可行方法。需要进一步的试验来提高反应率,并确定基于 DC 的疫苗接种在新的药物治疗时代的作用。

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