Measles to the Rescue: A Review of Oncolytic Measles Virus.
Measles to the Rescue: A Review of Oncolytic Measles Virus.
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DOI：
10.3390/v8100294
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发表时间：
2016-10-22
期刊：
影响因子：
--
通讯作者：
Fielding A
中科院分区：
文献类型：
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作者：
Aref S;Bailey K;Fielding A
溶瘤病毒治疗剂很可能成为癌症治疗的有力竞争者。麻疹病毒的疫苗株是一种在临床前试验中具有令人印象深刻的溶瘤活性范围的药剂，在早期临床试验中有越来越多的安全性和有效性证据。这种副粘病毒疫苗有一个被证明的安全记录，并且可以在实验室中进行仔细的基因修饰。麻疹病毒（MV）受体CD 46在许多肿瘤细胞中的过表达可能会引导病毒优先进入转化细胞，并且越来越多的人认识到nectin-4和信号淋巴细胞活化分子（SLAM）在溶瘤中的重要性。通过将肿瘤特异性配体的基因插入抗原如癌胚抗原（CEA）、CD 20、CD 38，并通过工程改造病毒以表达合成的微小RNA靶向序列，以及使病毒对天然病毒受体“盲化”，来重新靶向MV的成功尝试是增加病毒特异性和增强溶瘤作用的令人兴奋的措施。钠碘同向转运体（NIS）也可以由MV表达，这使得能够在体内追踪MV感染。使用MV-NIS的放射病毒疗法、将前药转化为其毒性代谢物的化学病毒疗法和包括掺入针对免疫检查点抑制剂的抗体的免疫病毒疗法也可以增加溶瘤潜力。抗病毒宿主免疫应答是MV成功的公认障碍，并且诸如通过载体细胞将MV运输到肿瘤部位的方法显示出希望。MV临床试验在卵巢癌、骨髓瘤和皮肤非霍奇金淋巴瘤方面取得了令人鼓舞的初步结果，目前在多形性胶质母细胞瘤、间皮瘤和鳞状细胞癌方面的开放试验的结果也令人热切期待。
Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA), CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and “blinding” the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS) can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated.
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DOI：
10.3181/00379727-86-21073
发表时间：
1954-01-01
影响因子：
--
作者：
ENDERS, JF;PEEBLES, TC;HOLLOWAY, A
通讯作者：
HOLLOWAY, A
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
6.4
作者：
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通讯作者：
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影响因子：
5.1
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