Antitumour activity of cationic-liposome-conjugated adenovirus containing the CCL 19 [chemokine (C-C motif) ligand 19] gene
Antitumour activity of cationic-liposome-conjugated adenovirus containing the CCL 19 [chemokine (C-C motif) ligand 19] gene
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DOI：
10.1042/ba20070038
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发表时间：
2007-10-01
影响因子：
2.8
通讯作者：
Wei, Yu-quan
中科院分区：
文献类型：
--
作者：
Cao, Mei;Deng, Hong-Xin;Wei, Yu-quan
CCL 19 [趋化因子（C-C基序）配体19;也称为MIP-3 β（巨噬细胞炎性蛋白-3 β）或ELC（EB病毒诱导的分子I配体趋化因子）]，免疫刺激细胞因子之一，化学吸引DC（树突状细胞）和T淋巴细胞。腺病毒载体因其较高的基因转染效率而成为肿瘤治疗中最常用的基因载体之一。然而，其更广泛的应用是有限的，由于免疫反应，减少转基因表达和降低重复给药的疗效。我们构建了含CCL 19基因的重组复制缺陷型腺病毒载体（Ad-CCL 19），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（Ad-CCL 19/PEG-PE）结合，用于小鼠纤维肉瘤的免疫治疗。虽然在第二次给药时观察到Ad-CCL 19和Ad-CCL 19/ PEG-PE治疗的小鼠之间几乎没有任何治疗差异，但最终结果表明AdCCL 19/PEG-PE治疗的小鼠存活时间更长。逆转录PCR和ELISA检测结果显示，Ad-CCL 19/PEG-PE治疗组的抗肿瘤效果可能与末次给药后高水平的CCL 19以及IFN-γ（干扰素-γ）和IL-12（白细胞介素-12）的持续表达有关。结果表明，PE阳离子脂质体结合腺病毒可以延长治疗基因在体内的表达，并可能提高抗肿瘤疗效。
CCL19 [chemokine (C-C motif) ligand 19; also known as MIP-3 beta (macrophage inflammatory protein-3 beta) or ELC (Epstein-Barr-virus-induced molecule I 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)-phosphaticlylethanolamine]-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 AdCCL19/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 (interieukin-12) in the Ad-CCL19/PEG-PE-treated group, which were measured by reverse-transcription PCR and ELISA. The results demonstrated that PE-cationic-liposome-conjugated adenovirus could prolong the expression of the therapeutic gene in vivo and may enhance the antitumour efficacy.