Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts.
Immunotherapy for patients with acute myeloid leukemia using autologous dendritic cells generated from leukemic blasts.
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使用白血病母细胞产生的自体树突状细胞对急性髓系白血病患者进行免疫治疗。
DOI：
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发表时间：
2006
影响因子：
5.2
通讯作者：
M. Schmitt
中科院分区：
文献类型：
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作者：
Li Li;K. Giannopoulos;P. Reinhardt;J. Tabarkiewicz;A. Schmitt;J. Greiner;J. Roliński;I. Hus;A. Dmoszyńska;M. Wiesneth;M. Schmitt
树突状细胞（DCs）是白血病细胞的专职抗原提呈细胞，其免疫接种可诱导急性髓系白血病（AML）患者产生抗白血病T细胞应答。为了检验这一假设，在良好生产规范（GMP）条件下产生自体AML-DC并皮下注射。在5名AML患者中进行最多4次，每两周一次。未观察到严重的不良副作用。3例患者病情稳定5.5-13个月，2例患者死于快速进展的AML。与初始T细胞频率相比，酶联免疫吸附斑点（ELISPOT）测定揭示了颗粒酶B释放特异性识别PRAME衍生肽（PRAME VDSLFFL）（AML母细胞表达的白血病相关抗原）的CD 8 + T细胞的显著增加。通过细胞因子珠测定评估的疫苗接种AML患者血清中的细胞因子水平在疫苗接种期间变化为升高的1型T辅助细胞模式。在接种过程中，CD 4 + T辅助细胞产生的干扰素γ增加。总之，我们证明了自体AML-DC疫苗接种具有良好的耐受性，并且可以导致AML患者中细胞毒性T细胞的增强和特异性应答。
Vaccination with dendritic cells (DCs) as professional antigen presenting cells generated from autologous leukemic blasts might elicit anti-leukemic T cell responses in patients with acute myeloid leukemia (AML). To test this hypothesis, autologous AML-DC were generated under good manufacturing practice (GMP) conditions and injected s.c. into five AML patients up to four times at a biweekly interval. No severe adverse side effects were observed. Three patients remained in a stable condition for 5.5-13 months and two patients died from rapidly progressive AML. Compared to the initial T cell frequency, enzyme linked immunosorbent spot (ELISPOT) assays revealed a significant increase of granzyme B releasing CD8+ T cells specifically recognizing the PRAME derived peptide (ALYVDSLFFL), a leukemia associated antigen expressed by AML blasts. The cytokine levels in the serum of vaccination AML patients as assessed by cytokine bead assay changed over the period of vaccination to an elevated type 1 T helper cell pattern. Interferon gamma production by CD4+ T helper cells increased during vaccination. In summary, we demonstrated that autologous AML-DC vaccination is well tolerated and can result in an enhanced and specific response of cytotoxic T cells in AML patients.