肝癌是严重威胁人类健康的恶性肿瘤，目前的治疗方式总体疗效仍不满意。我们前期研究首次报道了转染自杀基因的异基因CIK细胞（aCIK）有明显抗HCC的作用，自杀基因前体药物可有效预防异体反应的主要并发症GvHD，揭示了aCIK治疗实体肿瘤的可能性。而提高HCC治疗效果的关键环节是如何实现aCIK的HCC靶向性：我们将首次研究提高aCIK的趋肝性而增加对HCC靶向性杀伤作用。趋化因子12（SDF-1）及其特异受体CXCR4构成的SDF-1/CXCR4轴能诱导淋巴细胞的定向迁移及肿瘤细胞肝转移，利用索拉菲尼抗VEGF作用诱导的HCC及癌旁组织缺氧环境下 SDF-1的高表达，对aCIK细胞转染SDF-1的特异受体CXCR4，通过SDF-1/CXCR4轴的导航作用，实现效应aCIK的趋肝性迁移，协同索拉菲尼发挥更强大的抗HCC作用。本研究具有好的研究基础及创新性，可为肝癌的综合治疗提供新的有效方式。

Hepatocellular carcinoma（HCC）is a serious threat to human health, while the overall efficacy of the current treatment is still unsatisfied. Our previously study has reported that allogeneic cytokine-induced killer cells(aCIK) transduced with suicide gene had significant anti-HCC effect, importantly, administration of the suicide gene’s prodrug allows providing a safe and effective prevention of the major complications of aCIK’s alloreactivity, graft versus host disease (GvHD), therefore demonstrated proof-of-concept of using aCIK to treat solid tumors. The key to improve the treatment effect of HCC is how to achieve the HCC targeted of aCIK : we will first study to improve the ability of aCIK hepatic homing in order to increase antitumor effect on HCC. Chemotactic factor 12 (SDF-1) and its specific receptor CXCR4 constitutes of the SDF-1 / CXCR4 axis which can induce lymphocyte directed migration and hepatic metastasis of several kind of tumor cells. Utilizing the high expression level of SDF-1 in hypoxia environment of HCC as well as adjacent cancerous tissue during the course of anti-VEGF effect of sorafenib against HCC, we plan to transduce aCIK cells with CXCR4 in order to increase aCIK homing property to the tumor location of HCC through the navigation function of SDF-1 / CXCR4 axis, thus provide a more stronger anti-HCC effect together with sorafenib. The present project has good research foundation and innovation, could provide a new effective method of adoptive cellular immunotherapy for the treatment of HCC and, finally, represents good perspectives of clinical application.