combined therapy with cytokine-induced killer cells and oncolytic adenovirus expressing il-12 induce enhanced antitumor activity in liver tumor model结合疗法和细胞因子诱导的杀伤细胞和溶瘤腺病毒表达il - 12肝肿瘤模型中诱导增强的抗肿瘤活性.pdf

Combined Therapy with Cytokine-Induced Killer Cells and Oncolytic Adenovirus Expressing IL-12 Induce Enhanced Antitumor Activity in Liver Tumor Model 1. 1. 1. 1 1 1 1 Zhi Yang , Qianzhen Zhang , Ke Xu , Juanjuan Shan , Junjie Shen , Limei Liu , Yanmin Xu , 2 2 1 1 1 1 Feng Xia , Ping Bie , Xia Zhang , Youhong Cui , Xiu-wu Bian , Cheng Qian * 1 Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China, 2 Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing, China Abstract Both adoptive immunotherapy and gene therapy hold a great promise for treatment of malignancies. However, these strategies exhibit limited anti-tumor activity, when they are used alone. In this study, we explore whether combination of cytokine-induced killer (CIK) adoptive immunotherapy with oncolytic adenovirus-mediated transfer of human interleukin-12 (hIL-12) gene induce the enhanced antitumor potency. Our results showed that oncolytic adenovirus carrying hIL-12 (AdCN205-IL12) could produce high levels of hIL-12 in liver cancer cells, as compared with replication-defective adenovirus expressing hIL-12 (Ad-IL12). AdCN205-IL12 could specifically induce cytotoxocity to liver cancer cells. Combination of CIK cells with AdCN205-IL12 could induce higher antitumor activity to liver cancer cells in vitro than that induced by either CIK or AdCN205-IL12 alone, or combination of CIK and control vector AdCN205-GFP. Furthermore, treatment of the established liver tumors with the combined therapy of CIK cells