Wang Zheng, Li Pei, Xu Qinhong, Xu Jun, Li Xuqi, Zhang Xufeng, Ma Qingyong, Wu Zheng
Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
PLoS One. 2013 Jun 18;8(6):e66659. doi: 10.1371/journal.pone.0066659. Print 2013.
Hepatocellular carcinoma is one of the most common malignant neoplasms in the world and is the main cause of death in patients with liver cirrhosis. Surgical intervention is not suitable for majority of hepatocellular carcinoma. Investigation of the effective targeting to the tumor cells is essential for both primary tumors and metastases. Tumor specific cytotoxic T lymphocytes (CTL) have been considered to be the attractive vehicles for delivering therapeutic agents toward various tumor diseases. This study was to explore the distribution pattern of CTL carrying the lentiviral vectors with the characteristic of adenoviral E1 gene under the control of the cell activation-dependent CD40 ligand promoter (Lenti/hCD40L/E1AB). Following transduction with adenoviral vectors containing chimeric type 5 and type 35 fiber proteins (Ad5/35-TRAIL), these CTLs produced infectious virus when exposed to HepG2 cells. We assessed the therapeutic ability of CTLs using MTT, Western blot and colony formation assay. The novel CTL harboring Lenti/hCD40L/E1AB and Ad5/35-TRAIL caused proliferation inhibition and significant apoptosis in hepatocellular carcinoma cell lines. Thus, the novel CTL may be useful for the development of gene therapy approaches to hepatocellular carcinoma.
肝细胞癌是世界上最常见的恶性肿瘤之一，也是肝硬化患者的主要死因。大多数肝细胞癌患者不适合手术干预。对肿瘤细胞进行有效靶向研究对于原发性肿瘤和转移瘤都至关重要。肿瘤特异性细胞毒性T淋巴细胞（CTL）被认为是向各种肿瘤疾病递送治疗药物的有吸引力的载体。本研究旨在探索携带慢病毒载体的CTL在细胞活化依赖性CD40配体启动子（Lenti/hCD40L/E1AB）控制下具有腺病毒E1基因特征的分布模式。在用含有嵌合5型和35型纤维蛋白的腺病毒载体（Ad5/35-TRAIL）转导后，这些CTL在暴露于HepG2细胞时产生感染性病毒。我们使用MTT、蛋白质印迹和集落形成试验评估了CTL的治疗能力。携带Lenti/hCD40L/E1AB和Ad5/35-TRAIL的新型CTL导致肝癌细胞系增殖抑制和显著凋亡。因此，新型CTL可能有助于开发肝细胞癌的基因治疗方法。
