Cao Mei, Deng Hong-Xin, Zhao Jian, Fan Lin-yu, Jiang Yu, Wen Yan-Jun, Li Jiong, Lei Song, Mao Yong-qiu, Ding Zhen-Yu, Wei Yu-quan
Key Laboratory of Biological Resource and Ecological Environment of the Ministry of Education, College of Life Science, Sichuan University, Chengdu 610064, People's Republic of China.
Biotechnol Appl Biochem. 2007 Oct;48(Pt 2):109-16. doi: 10.1042/ba20070038.
CCL19 [chemokine (C-C motif) ligand 19; also known as MIP-3beta (macrophage inflammatory protein-3beta) or ELC (Epstein-Barr-virus-induced molecule 1 ligand chemokine)], one of the immunostimulatory cytokines, chemoattracts both DCs (dendritic cells) and T-lymphocytes. Adenoviral vector is one of the most used gene delivery vectors for cancer therapy because of its high gene-transfection efficiency. However, its wider application is limited, owing to immune responses that reduce transgene expression and decrease the efficacy of repeated administration. We constructed the recombinant replication deficient adenoviral vectors containing the CCL19 gene (Ad-CCL19) and combined them with PEG-PE [poly(ethylene glycol)-phosphatidylethanolamine]-modified cationic liposomes (Ad-CCL19/PEG-PE) for immunotherapy against murine fibrosarcoma. Although there were hardly any therapeutic differences between Ad-CCL19- and Ad-CCL19/PEG-PE-treated mice that were observed at the second administration, the final results demonstrated that Ad-CCL19/PEG-PE-treated mice survived much longer. The antitumour efficacy may be related to the high level of CCL19 after the final administration and lasting expression of IFN-gamma (interferon-gamma) and IL-12 (interleukin-12) in the Ad-CCL19/PEG-PE-treated group, which were measured by reverse-transcription PCR and ELISA. The results demonstrated that PEG-PE-cationic-liposome-conjugated adenovirus could prolong the expression of the therapeutic gene in vivo and may enhance the antitumour efficacy.
CCL19[趋化因子（C-C基序）配体19；也称为巨噬细胞炎性蛋白-3β（MIP-3β）或EB病毒诱导分子1配体趋化因子（ELC）]是一种免疫刺激细胞因子，可趋化树突状细胞（DC）和T淋巴细胞。腺病毒载体因其高基因转染效率，是癌症治疗中最常用的基因递送载体之一。然而，由于免疫反应会降低转基因表达并降低重复给药的疗效，其更广泛的应用受到限制。我们构建了含CCL19基因的重组复制缺陷型腺病毒载体（Ad-CCL19），并将其与聚乙二醇-磷脂酰乙醇胺（PEG-PE）修饰的阳离子脂质体相结合（Ad-CCL19/PEG-PE），用于对小鼠纤维肉瘤进行免疫治疗。尽管在第二次给药时未观察到Ad-CCL19和Ad-CCL19/PEG-PE治疗的小鼠之间有任何治疗差异，但最终结果表明，Ad-CCL19/PEG-PE治疗的小鼠存活时间长得多。抗肿瘤疗效可能与最终给药后CCL19的高水平以及Ad-CCL19/PEG-PE治疗组中γ干扰素（IFN-γ）和白细胞介素-12（IL-12）的持续表达有关，这通过逆转录PCR和酶联免疫吸附测定法进行测定。结果表明，PEG-PE阳离子脂质体偶联腺病毒可在体内延长治疗基因的表达，并可能增强抗肿瘤疗效。
