a Medicine/Division of Hematology and Oncology, University of Alabama at Birmingham , Birmingham , AL , USA.
b Medicine, University of Alabama at Birmingham , Birmingham , AL , USA.
Hum Vaccin Immunother. 2018 Apr 3;14(4):839-846. doi: 10.1080/21645515.2017.1412896. Epub 2018 Feb 22.
Oncolytic viruses represent a novel drug class in which native or modified viruses mediate tumor regression through selective replication within and lysis of tumor cells as well as induction of systemic antitumor immunity capable of eradicating tumor at distant, uninjected sites. Talimogene laherparepvec (TVEC) is a type I herpes simplex virus genetically modified to preferentially replicate in tumor cells, enhance antigen loading of MHC class I molecules and express granulocyte-macrophage colony-stimulating factor to increase tumor-antigen presentation by dendritic cells. It is presently the only oncolytic virus approved by the FDA with an indication for advanced melanoma based upon improved durable response rate in a randomized, phase III trial. Clinical trials are underway in melanoma investigating TVEC as neoadjuvant monotherapy and in combination with checkpoint inhibitors for unresectable disease as well as in an array of other malignancies. It is appropriate to review TVEC's biology mechanism of action, clinical indication and future directions as a prototype of the burgeoning class of oncolytic viruses.
溶瘤病毒代表了一类新型药物，其中天然或修饰的病毒通过在肿瘤细胞内选择性复制以及裂解肿瘤细胞，并诱导全身性抗肿瘤免疫来介导肿瘤消退，从而能够消除远处未注射部位的肿瘤。Talimogene laherparepvec（TVEC）是一种经过基因改造的 I 型单纯疱疹病毒，能够优先在肿瘤细胞中复制，增强 MHC Ⅰ类分子的抗原加载，并表达粒细胞-巨噬细胞集落刺激因子，从而增加树突状细胞对肿瘤抗原的呈递。它是目前唯一一种获得 FDA 批准的溶瘤病毒，适应症为晚期黑色素瘤，基于随机、III 期临床试验中持久性应答率的改善。目前正在黑色素瘤中开展临床试验，研究 TVEC 作为新辅助单药治疗以及与检查点抑制剂联合用于不可切除疾病的治疗，以及一系列其他恶性肿瘤的治疗。作为新兴的溶瘤病毒类别的原型，有必要对 TVEC 的生物学作用机制、临床适应证和未来方向进行综述。
