Replicating retroviral vectors for oncolytic virotherapy of experimental hepatocellular carcinoma.
Replicating retroviral vectors for oncolytic virotherapy of experimental hepatocellular carcinoma.
复制标题
复制逆转录病毒载体用于实验性肝细胞癌的溶瘤病毒疗法。
DOI：
10.3892/or.2012.1789
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Chien
中科院分区：
文献类型：
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作者：
Yin‐Che Lu;Ying;Yuan Yu;Yi;Jen;Yu;Cheng;Chien
基于鼠白血病病毒（MLV）的复制逆转录病毒载体（RRV）介导的基因治疗先前被证明在杀死肿瘤细胞方面非常有效，从而显着抑制体内肿瘤生长。最近，我们开发了一种不同形式的 RRV，它源自另一种逆转录病毒，长臂猿白血病病毒 (GALV)，作为癌症治疗剂。我们比较了两种类型 RRV 在实验性肝细胞癌 (HCC) 中的基因递送效率和抗肿瘤效果。我们的结果表明，两种 RRV 都可以在体外有效地扩散到整个 HCC 细胞群，并在体内 HCC 异种移植物中实现高转导效率，而 GALV RRV 通常在肿瘤中表现出更快的复制动力学。在体外，即使最初只有 1% 的 HCC 细胞产生表达酵母胞嘧啶脱氨酶自杀基因的 RRV，也能实现大量的 HCC 细胞杀伤，这表明 RRV 复制扩散所实现的基因转移的高效率大大增加了自杀基因的毒性。在体内，GALV RRV介导的自杀基因疗法有效抑制了HCC肿瘤的生长，并且在肿瘤外组织中没有观察到可检测到的RRV信号，这显示出使用GALV RRV作为癌症治疗剂的前景。
Gene therapy mediated by murine leukemia virus (MLV)-based replicating retrovirus vector (RRV) was previously proven to be highly effective in tumor cell killing, resulting in significant suppression of tumor growth in vivo. Recently, we developed a different form of RRV which is derived from another retrovirus, gibbon ape leukemia virus (GALV), as a cancer therapeutic agent. We compared the gene delivery efficiency and antitumor effects in the two types of RRV in experimental hepatocellular carcinoma (HCC). Our results show that both RRVs can efficiently spread throughout entire HCC cell populations in vitro and achieve high transduction efficiency in HCC xenografts in vivo, while GALV RRV, in general, exhibited more rapid replication kinetics in the tumors. In vitro, substantial HCC cell killing was achieved even when initially only 1% of the HCC cells were producing RRVs that express the yeast cytosine deaminase suicide gene, indicating that the high efficiency of gene transfer by replicative spread of RRVs greatly increased suicide gene toxicity. In vivo, GALV RRV-mediated suicide gene therapy efficiently suppressed HCC tumor growth and no detectable RRV signals were observed in extratumoral tissues, showing promise in using GALV RRV as a cancer therapeutic agent.