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本妥昔单抗(SGN-35)联合细胞因子诱导的杀伤细胞治疗淋巴瘤的疗效增强

Increased Efficacy of Brentuximab Vedotin (SGN-35) in Combination with Cytokine-Induced Killer Cells in Lymphoma.

作者信息

Esser Laura, Weiher Hans, Schmidt-Wolf Ingo

机构信息

Center for Integrated Oncology (CIO), Medizinische Klinik und Poliklinik III, University of Bonn, Sigmund-Freud-Straße 25, 53105 Bonn, Germany.

Hochschule Bonn-Rhein-Sieg, 53359 Rheinbach, Germany.

出版信息

Int J Mol Sci. 2016 Jul 1;17(7):1056. doi: 10.3390/ijms17071056.

DOI:10.3390/ijms17071056
PMID:27376285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4964432/
Abstract

Brentuximab vedotin (SGN-35) is an antibody-drug conjugate with a high selectivity against CD30⁺ cell lines and more than 300-fold less activity against antigen-negative cells. In the last years, the results of many in vitro and in vivo studies have led to the fast approval of this drug to treat lymphoma patients. Another innovative method to treat tumor cells including lymphoma cells is the use cytokine-induced killer (CIK) cells, which have also been approved and proven to be a safe treatment with only minor adverse events. In this study, a possible additive effect when combining SGN-35 with CIK cells was investigated. The combinational treatment showed that it reduces the viability of CD30⁺ cell lines significantly in vitro. Additionally, the amount of lymphoma cells was significantly reduced when exposed to CIK cells as well as when exposed to SGN-35. A significant negative effect of SGN-35 on the function of CIK cells could be excluded. These results lead to the assumption that SGN-35 and CIK cells in combination might achieve better results in an in vitro setting compared to the single use of SGN-35 and CIK cells. Further investigations in in vivo models must be conducted to obtain a better understanding of the exact mechanisms of both treatments when applied in combination.

摘要

本妥昔单抗(SGN-35)是一种抗体药物偶联物,对CD30⁺细胞系具有高选择性,对抗原阴性细胞的活性低300多倍。在过去几年中,许多体外和体内研究的结果促使该药物迅速获批用于治疗淋巴瘤患者。另一种治疗包括淋巴瘤细胞在内的肿瘤细胞的创新方法是使用细胞因子诱导杀伤(CIK)细胞,CIK细胞也已获批并被证明是一种安全性良好、仅有轻微不良事件的治疗方法。在本研究中,我们研究了SGN-35与CIK细胞联合使用时可能产生的相加效应。联合治疗显示,它在体外能显著降低CD30⁺细胞系的活力。此外,暴露于CIK细胞以及暴露于SGN-35时,淋巴瘤细胞的数量均显著减少。可以排除SGN-35对CIK细胞功能的显著负面影响。这些结果表明,与单独使用SGN-35和CIK细胞相比,在体外环境中,SGN-35与CIK细胞联合使用可能会取得更好的效果。必须在体内模型中进行进一步研究,以更好地了解两种治疗联合应用时的确切机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/10665efbece5/ijms-17-01056-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/a1abf3b35ba8/ijms-17-01056-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/10665efbece5/ijms-17-01056-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/5c57244b69db/ijms-17-01056-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/351308bfc52d/ijms-17-01056-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/a1abf3b35ba8/ijms-17-01056-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ecf/4964432/10665efbece5/ijms-17-01056-g004.jpg

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The combination of dendritic cells-cytotoxic T lymphocytes/cytokine-induced killer (DC-CTL/CIK) therapy exerts immune and clinical responses in patients with malignant tumors.树突状细胞-细胞毒性T淋巴细胞/细胞因子诱导的杀伤细胞(DC-CTL/CIK)联合疗法在恶性肿瘤患者中产生免疫和临床反应。
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