McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
McMaster Immunology Research Center, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada; Ontario Veterinary College, University of Guelph, Toronto, Ontario, Canada.
Mol Ther. 2014 Feb;22(2):420-429. doi: 10.1038/mt.2013.249. Epub 2013 Oct 25.
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.
水疱病毒马利巴最近被鉴定为一种有效的溶瘤病毒。在本研究中，我们构建了一种减毒马利巴株，定义为 MG1，以表达一种黑色素瘤相关肿瘤抗原。在无肿瘤和黑色素瘤荷瘤小鼠中评估了其诱导抗肿瘤免疫的能力。单独使用时，MG1 疫苗似乎不足以诱导针对肿瘤抗原的可检测适应性免疫。然而，当用作异源初免-加强方案中的加强载体时，MG1 疫苗迅速产生了强烈的抗原特异性 T 细胞免疫应答。一旦用于治疗同源性鼠黑色素瘤肿瘤，我们的溶瘤初免-加强免疫接种方案涉及马利巴 MG1，显著延长了中位生存期，并使 20%以上接受治疗的动物完全缓解。这项工作将马利巴病毒 MG1 描述为一种具有溶瘤活性和显著增强适应性抗肿瘤免疫能力的强力癌症免疫治疗疫苗载体。
