Cross-priming of CD8+ T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia
Cross-priming of CD8+ T cells in vivo by dendritic cells pulsed with autologous apoptotic leukemic cells in immunotherapy for elderly patients with acute myeloid leukemia
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DOI：
10.1016/j.exphem.2011.01.001
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发表时间：
2011-04-01
影响因子：
2.6
通讯作者：
Uchiyama, Takashi
中科院分区：
文献类型：
--
作者：
Kitawaki, Toshio;Kadowaki, Norimitsu;Uchiyama, Takashi
目标。老年急性髓系白血病(AML)患者的预后仍然很差。为了探索免疫治疗改善这些患者临床预后的潜力，我们对老年急性髓细胞白血病患者进行了基于树突状细胞(DC)的免疫治疗的I期临床试验。材料和方法。化疗减轻肿瘤负荷后获得自体单核细胞。在粒-巨噬细胞集落刺激因子和白介素4诱导下，以自体凋亡的白血病细胞为抗原冲击未成熟DC。每隔2周对4名患者进行5次皮内注射DCs。为了促进DC向淋巴结的迁移，注射部位前一天用灭活化脓性链球菌OK-432进行预处理。将DCs与OK-432共注射，在体内诱导成熟和产生IL-12。在四名患者中，有两名患者的抗白血病反应是通过干扰素-伽玛酶联免疫斑点试验或四聚体试验观察的。在一例人类白细胞抗原A52402阳性的患者中，观察到CD8(+)T细胞对WT1和人端粒酶逆转录酶衍生多肽的反应，表明体内存在交叉启动。具有抗白血病免疫力的两名患者的病情稳定期明显长于其他两名患者。本研究证实了在老年AML患者体内，从自体凋亡的白血病细胞中交叉呈递白血病相关抗原的自体DC具有免疫原性。2011年ISEH--血液学和干细胞学会。由爱思唯尔公司出版。
Objective. The prognosis for elderly patients with acute myeloid leukemia (AML) remains dismal. To explore the potential of immunotherapy for improving clinical outcomes for these patients, we performed a phase I clinical trial of dendritic cell (DC) based immunotherapy for elderly patients with AML.Materials and Methods. Autologus monocytes were obtained after reducing tumor burden by chemotherapy. Immature DCs induced with granulocyte-macrophage colony-stimulating factor and interleukin-4 were pulsed with autologous apoptotic leukemic cells as antigens. DCs were administered intradermally to four patients five times at 2-week intervals. To facilitate DC migration to lymph nodes, injection sites were pretreated with killed Streptococcus pyogenes OK-432 one day before. DCs were coinjected with OK-432 to induce maturation and interleukin-12 production in vivo.Results. Antileukemic responses were observed by an interferon-gamma enzyme-linked immunospot assay or a tetramer assay in two of four patients. In a human leukocyte antigen A52402-positive patient, induction of CD8(+) T-cell responses to WT1- and human telomerase reverse transcriptase derived peptides were observed, indicating cross-priming in vivo. The two patients with antileukemic immunity showed longer periods of disease stabilization than the other two patients.Conclusions. This study demonstrates the immunogenicity of autologous DCs that cross-present leukemia-associated antigens from autologous apoptotic leukemic cells in vivo in elderly patients with AML. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.