Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus.
Highly efficient tumor transduction and antitumor efficacy in experimental human malignant mesothelioma using replicating gibbon ape leukemia virus.
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DOI：
10.1038/cgt.2013.67
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发表时间：
2013-12
影响因子：
6.4
通讯作者：
Kasahara N
中科院分区：
文献类型：
--
作者：
Kubo S;Takagi-Kimura M;Logg CR;Kasahara N
逆转录病毒复制载体（RRV）已被证明在多种癌症模型中实现有效的肿瘤转导和增强的治疗益处。在这里，我们评估了两种不同的RRV来源于嗜酸性小鼠白血病病毒（AMLV）和巨猿白血病病毒（GALV），在人类恶性间皮瘤细胞。在体外，表达绿色荧光蛋白基因的两种RRV在大多数间皮瘤细胞系中有效复制，但在正常间皮瘤细胞中没有。值得注意的是，在不允许AMLV-RRV的ACC-MESO-1间皮瘤细胞中，通过体内荧光成像，GALV-RRV可以在培养物中和具有皮下异种移植物的小鼠中有效地扩散。其次，与AMLV-RRV相比，表达胞嘧啶脱氨酶前药激活剂基因的GALV-RRV显示出以前药5-氟胞嘧啶剂量依赖性方式有效地杀死ACC-MESO-1细胞。GALV-RRV介导的前药激活剂基因治疗在裸鼠皮下ACC-MESO-1肿瘤生长中实现了显著的抑制。定量逆转录PCR表明，ACC-MESO-1细胞表达较高的PiT-1（GALV受体）和较低的PiT-2（AMLV受体）相比，正常间皮瘤细胞和其他间皮瘤细胞，大概解释了独特的发现，GALV-RRV复制比AMLV-RRV在这些细胞中更稳健。这些数据表明GALV-RRV介导的前体药物激活剂基因疗法在间皮瘤治疗中的潜在效用。
Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor transduction and enhanced therapeutic benefit in a wide variety of cancer models. Here we evaluated two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV), in human malignant mesothelioma cells. In vitro, both RRVs expressing the green fluorescent protein gene efficiently replicated in most mesothelioma cell lines tested, but not in normal mesothelial cells. Notably, in ACC-MESO-1 mesothelioma cells that were not permissive for AMLV-RRV, the GALV-RRV could spread efficiently in culture and in mice with subcutaneous xenografts by in vivo fluorescence imaging. Next, GALV-RRV expressing the cytosine deaminase prodrug activator gene showed efficient killing of ACC-MESO-1 cells in a prodrug 5-fluorocytosine dose-dependent manner, compared with AMLV-RRV. GALV-RRV-mediated prodrug activator gene therapy achieved significant inhibition of subcutaneous ACC-MESO-1 tumor growth in nude mice. Quantitative reverse transcription PCR demonstrated that ACC-MESO-1 cells express higher PiT-1 (GALV receptor) and lower PiT-2 (AMLV receptor) compared with normal mesothelial cells and other mesothelioma cells, presumably accounting for the distinctive finding that GALV-RRV replicates much more robustly than AMLV-RRV in these cells. These data indicate the potential utility of GALV-RRV-mediated prodrug activator gene therapy in the treatment of mesothelioma.
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影响因子：
3.5
作者：
Kubo, Shuji;Kawasaki, Yoshiko;Yamaoka, Norie;Tagawa, Masatoshi;Kasahara, Noriyuki;Terada, Nobuyuki;Okamura, Haruki
通讯作者：
Okamura, Haruki
影响因子：
5.3
作者：
MILLER, DG;ADAM, MA;MILLER, AD
通讯作者：
MILLER, AD
影响因子：
3.5
作者：
Adusumilli, Prasad S.;Stiles, Brendon M.;Fong, Yuman
通讯作者：
Fong, Yuman
影响因子：
4.2
作者：
Wang, WJ;Tai, CK;Chen, TC
通讯作者：
Chen, TC
影响因子：
5.4
作者：
Logg, CR;Logg, A;Kasahara, N
通讯作者：
Kasahara, N