A Phase I-II Study of α-Galactosylceramide-Pulsed IL-2/GM-CSF-Cultured Peripheral Blood Mononuclear Cells in Patients with Advanced and Recurrent Non-Small Cell Lung Cancer
A Phase I-II Study of α-Galactosylceramide-Pulsed IL-2/GM-CSF-Cultured Peripheral Blood Mononuclear Cells in Patients with Advanced and Recurrent Non-Small Cell Lung Cancer
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DOI：
10.4049/jimmunol.0800126
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发表时间：
2009-02-15
影响因子：
4.4
通讯作者：
Nakayama, Toshinori
中科院分区：
文献类型：
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作者：
Motohashi, Shinichiro;Nagato, Kaoru;Nakayama, Toshinori
为了评估用IL-2和GM-CSF （IL-2/GM-CSF培养的PBMC）培养的a-半乳糖神经酰胺（α GalCer） krn7000脉冲PBMC的安全性、免疫反应和抗肿瘤反应，在非小细胞肺癌患者中进行了一项I-II期研究。晚期非小细胞肺癌或复发性肺癌患者对标准治疗无效。α - galcer脉冲IL-2/ gm - csf培养的PBMCs (1 × 10（9)/m(2)）静脉注射4次。每周监测免疫反应。23例患者入组，17例（73.9%）完成研究。未观察到与治疗相关的严重不良事件。注射agalcer脉冲IL-2/ gm - csf培养的PBMCs后，10例患者（58.8%）外周血中ifn - γ生成细胞数量增加。5例病情稳定，其余12例病情进展。17例患者的估计中位生存时间（MST）为18.6个月（范围为3.8至36.3个月）。10例显示ifn - γ生成细胞增加的患者（>= 2倍）显示MST延长（31.9个月，范围14.5至36.3个月），而不良反应患者（n = 7） MST延长（9.7个月，范围3.8至25.0个月）（对数秩检验，p = 0.0015）。agaler脉冲IL-2/ gm - csf培养的PBMCs耐受良好，并伴有NKT细胞依赖性免疫应答的成功诱导。在PBMCs中，aGalCer刺激导致的ifn - γ生成细胞的增加与MST的延长显著相关。这些结果令人鼓舞，值得进一步评估这种免疫疗法的生存效益。免疫学杂志，2009,32(2):2492-2501。
To evaluate the safety, immune responses, and antitumor responses after the administration of a-galactosylceramide (alpha GalCer) KRN7000-pulsed PBMC cultured with IL-2 and GM-CSF (IL-2/GM-CSF-cultured PBMCs), a phase I-II study in patients with non-small cell lung cancer was conducted. Patients with advanced non-small cell lung cancer or recurrent lung cancer refractory to the standard therapy were eligible. alpha GalCer-pulsed IL-2/GM-CSF-cultured PBMCs (I X 10(9)/m(2)) were i.v. administered four times. Immune responses were monitored weekly. Twenty-three patients were enrolled in this study and 17 cases (73.9%) completed. No severe adverse event related to the treatment was observed. After the injection of aGalCer-pulsed IL-2/GM-CSF-cultured PBMCs, an increased number of IFN-gamma-producing cells in the peripheral blood were detected in 10 patients (58.8%). Five cases remained as stable disease, and the remaining 12 cases were evaluated as progressive disease. The estimated median survival time (MST) of the 17 cases was 18.6 mo (range, 3.8 to 36.3 mo). Ten patients who displayed increased IFN-gamma-producing cells (>= 2-fold) showed prolonged MST (31.9 mo; range, 14.5 to 36.3 mo) as compared with poor-responder patients (n = 7) MST (9.7 mo; range, 3.8 to 25.0 mo) (log-rank test,p = 0.0015). The administration of aGalCer-pulsed IL-2/GM-CSF-cultured PBMCs was well tolerated and was accompanied by the successful induction of NKT cell-dependent immune responses. The increased IFN-gamma-producing cells that result from aGalCer stimulation in PBMCs were significantly associated with prolonged MST. These results are encouraging and warrant further evaluation for survival benefit of this immunotherapy. The Journal of Immunology, 2009, 182: 2492-2501.