Biederbick Kaja D, Schmidt-Wolf Ingo G H
Department of Internal Medicine III, University Hospital Bonn, D-53105 Bonn, Germany.
Department of Integrated Oncology, CIO Bonn, University Hospital Bonn, D-53105 Bonn, Germany.
Oncol Lett. 2019 Feb;17(2):2425-2430. doi: 10.3892/ol.2018.9849. Epub 2018 Dec 18.
Since the publication of a novel protocol in 1991, cytokine-induced killer (CIK) cells have shown promising results in the treatment against neoplastic diseases. Despite ongoing preclinical and clinical studies, CIK cell treatment in the context of human monoclonal antibodies targeting tumor-necrosis factor receptors remains overlooked. The present study investigated whether a combination of CIK cells with human monoclonal antibody anti-CD40 and anti-Glucocorticoid-induced TNF-related protein (GITR) would lead to further cytotoxicity against tumor cells expressing CD40 and GITR ligand (L). Therefore, experiments with human lymphoma cell lines SU-DHL-4 and Daudi (both CD40 positive) and human breast adenocarcinoma MCF-7 (GITRL positive) were performed and the secretion of interferon (IFN)-γ was measured. Three interesting results emerged: i) a combination of CIK cells and anti-CD40 mAb is more effective than CIK cell treatment alone; ii) the use of anti-GITR mAb and CIK cells significantly enhanced the cytotoxicity of CIK cells against MCF-7 compared with single CIK cell treatment and iii) the combination of both antibodies and CIK cells abrogates the anti tumoral effect of CIK cells on all three cell lines. By performing an ELISA for IFN-γ measurement, a lower secretion was observed when anti-CD40 or anti-GITR mAb was added. This outcome indicates that further studies and may aid in understanding the synergistic molecular mechanisms of CIK cells, and anti-CD40 and anti-GITR mAb.
自1991年一种新方案发表以来，细胞因子诱导的杀伤（CIK）细胞在肿瘤疾病治疗中已显示出有前景的结果。尽管临床前和临床研究仍在进行，但在针对肿瘤坏死因子受体的人单克隆抗体背景下的CIK细胞治疗仍被忽视。本研究调查了CIK细胞与人抗CD40单克隆抗体和抗糖皮质激素诱导的肿瘤坏死因子相关蛋白（GITR）的组合是否会导致对表达CD40和GITR配体（L）的肿瘤细胞产生进一步的细胞毒性。因此，对人淋巴瘤细胞系SU-DHL-4和Daudi（均为CD40阳性）以及人乳腺腺癌MCF-7（GITRL阳性）进行了实验，并测量了干扰素（IFN）-γ的分泌。出现了三个有趣的结果：i）CIK细胞和抗CD40单克隆抗体的组合比单独的CIK细胞治疗更有效；ii）与单独的CIK细胞治疗相比，使用抗GITR单克隆抗体和CIK细胞显著增强了CIK细胞对MCF-7的细胞毒性；iii）两种抗体和CIK细胞的组合消除了CIK细胞对所有三种细胞系的抗肿瘤作用。通过进行ELISA测量IFN-γ，当添加抗CD40或抗GITR单克隆抗体时，观察到较低的分泌。这一结果表明，进一步的研究可能有助于理解CIK细胞、抗CD40和抗GITR单克隆抗体的协同分子机制。
