Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes.

Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes.
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DOI:
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发表时间:
2008
影响因子:
2
通讯作者:
H. Kondo;S. Hazama;Toru Kawaoka;S. Yoshino;S. Yoshida;Kazuhisa Tokuno;M. Takashima;T. Ueno;
H. Kondo;S. Hazama;Toru Kawaoka;S. Yoshino;S. Yoshida;Kazuhisa Tokuno;M. Takashima;T. Ueno;
中科院分区:
医学4区
文献类型:
--
作者:
H. Kondo;S. Hazama;Toru Kawaoka;S. Yoshino;S. Yoshida;Kazuhisa Tokuno;M. Takashima;T. Ueno;

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背景胰腺癌预后不良。评价了使用MUC 1肽致敏的树突状细胞(MUC 1-DC)和用表达MUC 1的胰腺癌YPK-1致敏的细胞毒性T淋巴细胞(CTL)(MUC 1-CTL)的免疫治疗的临床疗效。患者和方法20例不能切除或复发的胰腺癌患者入组。将外周血单个核细胞(PBMC)分离成用于诱导MUC 1-DC的贴壁细胞和用于MUC 1-CTL的漂浮细胞。通过与粒细胞单核细胞集落刺激因子(GM-CSF)和白细胞介素-4(IL-4)一起培养,然后暴露于MUC 1肽和TNF-α来产生MUC 1-DC。通过与YPK-1共培养,然后与白细胞介素-2(IL-2)共培养来诱导MUC 1-CTL。皮内注射MUC 1-DC,静脉内给予MUC 1-CTL。结果治疗次数2 ~ 15次。1例多发性肺转移患者出现完全缓解。5例患者病情稳定。平均生存期9.8个月。未观察到II-IV级毒性。结论MUC 1-DC和MUC 1-CTL联合免疫治疗胰腺癌是可行和有效的。
BACKGROUND Pancreatic cancer has a poor prognosis. The clinical efficacy of immunotherapy using both dendritic cells pulsed with MUC1 peptide (MUC1-DC) and, cytotoxic T lymphocyte (CTL) sensitized with a pancreatic cancer, YPK-1, expressing MUC1 (MUC1-CTL) was evaluated. PATIENTS AND METHODS Twenty patients with unresectable or recurrent pancreatic cancer were enrolled. Peripheral blood mononuclear cells (PBMCs) were separated into adherent cells for induction of MUC1-DCs and floating cells for MUC1-CTLs. MUC1-DCs were generated by culture with granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) and then exposed to MUC1 peptide and TNF-alpha. MUC1-CTLs were induced by co-culture with YPK-1 and then with interleukin-2 (IL-2). MUC1-DCs were injected intradermally and MUC1-CTLs were given intravenously. RESULTS Patients were treated from 2 to 15 times. One patient with multiple lung metastases experienced a complete response. Five patients had stable disease. The mean survival time was 9.8 months. No grade II-IV toxicity was observed. CONCLUSION Adoptive immunotherapy with MUC1-DC and MUC1-CTL may be feasible and effective for pancreatic cancer.