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细胞因子诱导的杀伤细胞在急性早幼粒细胞白血病治疗过程中的归巢

Homing of cytokine-induced killer cells during the treatment of acute promyelocytic leukemia.

作者信息

Wang Hong, Cao Fenglin, Li Jinmei, Li Yong, Liu Xiuhua, Wang Lifan, Liu Zhiyu, Li Yang, Zhao Hui, Zhou Jin

机构信息

Department of Hematology and Central Laboratory, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, 150001, China.

出版信息

Int J Hematol. 2014 Aug;100(2):165-70. doi: 10.1007/s12185-014-1618-7. Epub 2014 Jun 15.

DOI:10.1007/s12185-014-1618-7
PMID:24929848
Abstract

Cytokine-induced killer (CIK) cells have been shown to be an effective immunotherapy for malignancies. However, their clinical application has been limited due to lack of knowledge on their in vivo kinesis. In this study, we explored their biodistribution by labeling CIK cells with (18)F-FDG and tracking their in vivo migration by PET/CT imaging. In the nine refractory APL patients enrolled in this study, pre-treatment PET/CT scans revealed leukemia burdens in vertebrae, and the bones of the pelvis and limbs. Post-treatment serial PET/CT tracked the localization of CIK cells over time: at 1 h, the majority of these cells accumulated diffusely in the lungs, while the first minor cell activities were observed in brain, liver and spleen; at 4 and 8 h, they not only migrated to the heart, spleen, and liver, but also showed tendencies to accumulate in bone marrow and brain. This specific cell migration route suggested that CIK cells show in vivo functional kinesis and potency as a targeted immunotherapy. The clinical outcome of this small cohort of nine patients supported the efficacy of this regimen: two patients achieved rapid complete remission after three-cycle treatment, and six patients remained stable, subsequently became sensitive to conventional therapy, and also achieved complete remission.

摘要

细胞因子诱导的杀伤(CIK)细胞已被证明是一种有效的恶性肿瘤免疫疗法。然而,由于对其体内运动情况了解不足,它们的临床应用受到了限制。在本研究中,我们通过用(18)F-FDG标记CIK细胞并利用PET/CT成像追踪其体内迁移来探索它们的生物分布。在本研究纳入的9例难治性急性早幼粒细胞白血病(APL)患者中,治疗前的PET/CT扫描显示椎骨、骨盆和四肢骨骼存在白血病负荷。治疗后的系列PET/CT随时间追踪CIK细胞的定位:1小时时,这些细胞大部分弥漫性积聚在肺部,而在脑、肝和脾中观察到首次轻微的细胞活性;4小时和8小时时,它们不仅迁移到心脏、脾和肝,而且还显示出在骨髓和脑中积聚的趋势。这种特定的细胞迁移途径表明CIK细胞在体内表现出功能性运动能力以及作为靶向免疫疗法的效力。这一小群9例患者的临床结果支持了该方案的疗效:2例患者在三个周期治疗后迅速完全缓解,6例患者病情保持稳定,随后对传统疗法变得敏感,并也实现了完全缓解。

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Thymoglobulin, interferon-γ and interleukin-2 efficiently expand cytokine-induced killer (CIK) cells in clinical-grade cultures.
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