Wu Tao, Leboeuf Céline, Durand Sarah, Su Bin, Deschamps Marina, Zhang Xiaowen, Ferrand Christophe, Pessaux Patrick, Robinet Eric
Department of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650500, P.R. China.
French National Institute of Health and Medical Research, Research Unit 1110, F-67000 Strasbourg, France.
Mol Med Rep. 2016 Mar;13(3):2645-54. doi: 10.3892/mmr.2016.4811. Epub 2016 Jan 27.
Adoptive immunotherapy using autologous cytokine-induced killer (CIK) cells reduces the recurrence rate of hepatocellular carcinoma (HCC) in association with transarterial chemoembolization or radiofrequency. However, a large‑scale development of this immunotherapy remains difficult to consider in an autologous setting, considering the logistical hurdles associated with the production of this cell therapy product. A previous study has provided the in vitro and in vivo proof‑of‑concept that allogeneic suicide gene‑modified killer cells (aSGMKCs) from healthy blood donors (a cell therapy product previously demonstrated to provide anti‑leukemic effects to patients receiving allogeneic hematopoietic transplantation) may exert a potent anti‑tumor effect towards HCC. Therefore, the development of a bank of 'ready‑for‑use' aSGMKCs was proposed as an approach allowing for the development of immunotherapies that are more convenient and on a broader scale than that of autologous therapies. In the present study, aSGMKCs were compared with CIK cells generated according to three different protocols. Similar to CIK cells, the cytotoxic activity of aSGMKCs toward the Huh‑7 HCC cell line was mediated by tumor necrosis factor‑related apoptosis‑inducing ligand, tumor necrosis factor‑α and interferon‑γ. Furthermore, the frequency of natural killer (NK), NK‑like T and T cells, and their in vitro and in vivo cytotoxicity activities were similar between aSGMKCs and CIK cells. Thus, the present study demonstrated that aSGMKCs are similar to CIK cells, further suggesting the possibility for future use of aSGMKCs in the treatment of solid tumors, including HCC.
采用自体细胞因子诱导的杀伤细胞（CIK）进行过继性免疫治疗，可降低与经动脉化疗栓塞或射频治疗相关的肝细胞癌（HCC）复发率。然而，考虑到这种细胞治疗产品生产过程中存在的后勤障碍，在自体环境下大规模开展这种免疫治疗仍难以实现。先前的一项研究已提供了体外和体内的概念验证，即来自健康献血者的同种异体自杀基因修饰的杀伤细胞（aSGMKC，一种先前已证明对接受同种异体造血移植的患者具有抗白血病作用的细胞治疗产品）可能对HCC发挥强大的抗肿瘤作用。因此，有人提出建立一个“即用型”aSGMKC库，作为一种比自体疗法更方便且能更广泛开展免疫治疗的方法。在本研究中，将aSGMKC与根据三种不同方案生成的CIK细胞进行了比较。与CIK细胞类似，aSGMKC对Huh-7 HCC细胞系的细胞毒活性是由肿瘤坏死因子相关凋亡诱导配体、肿瘤坏死因子-α和干扰素-γ介导的。此外，aSGMKC与CIK细胞之间自然杀伤（NK）细胞、NK样T细胞和T细胞的频率及其体外和体内细胞毒活性相似。因此，本研究表明aSGMKC与CIK细胞相似，进一步提示了未来aSGMKC用于治疗包括HCC在内的实体瘤的可能性。
