Maraba Virus as a Potent Oncolytic Vaccine Vector
Maraba Virus as a Potent Oncolytic Vaccine Vector
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DOI：
10.1038/mt.2013.249
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发表时间：
2014-02-01
影响因子：
12.4
通讯作者：
Lichty, Brian D.
中科院分区：
文献类型：
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作者：
Pol, Jonathan G.;Zhang, Liang;Lichty, Brian D.
马拉巴弹状病毒最近被定性为一种强效溶瘤病毒。在本研究中，我们设计了一种减毒 Maraba 菌株（定义为 MG1）来表达黑色素瘤相关肿瘤抗原。在无肿瘤和黑色素瘤小鼠中评估了其增强抗肿瘤免疫力的能力。单独使用 MG1 疫苗似乎不足以引发针对肿瘤抗原的可检测的适应性免疫。然而，当在异源初免-加强方案中用作加强载体时，MG1 疫苗迅速产生强烈的抗原特异性 T 细胞免疫反应。一旦应用于治疗同基因小鼠黑色素瘤肿瘤，我们涉及 Maraba MG1 的溶瘤初免加强疫苗接种方案可显着延长中位生存期，并允许超过 20% 的接受治疗的动物完全缓解。这项工作将马拉巴病毒 MG1 描述为一种用于癌症免疫治疗的有效疫苗载体，显示出溶瘤活性和增强适应性抗肿瘤免疫的显着能力。
The rhabdovirus Maraba has recently been characterized as a potent oncolytic virus. In the present study, we engineered an attenuated Maraba strain, defined as MG1, to express a melanoma-associated tumor antigen. Its ability to mount an antitumor immunity was evaluated in tumor-free and melanoma tumor-bearing mice. Alone, the MG1 vaccine appeared insufficient to prime detectable adaptive immunity against the tumor antigen. However, when used as a boosting vector in a heterologous prime-boost regimen, MG1 vaccine rapidly generated strong antigen-specific T-cell immune responses. Once applied for treating syngeneic murine melanoma tumors, our oncolytic prime-boost vaccination protocol involving Maraba MG1 dramatically extended median survival and allowed complete remission in more than 20% of the animals treated. This work describes Maraba virus MG1 as a potent vaccine vector for cancer immunotherapy displaying both oncolytic activity and a remarkable ability to boost adaptive antitumor immunity.