Immune System, Friend or Foe of Oncolytic Virotherapy?
Immune System, Friend or Foe of Oncolytic Virotherapy?
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DOI：
10.3389/fonc.2017.00106
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发表时间：
2017
影响因子：
4.7
通讯作者：
Dey M
中科院分区：
文献类型：
--
作者：
Filley AC;Dey M
溶瘤病毒（OV）是一类新兴的靶向抗癌疗法，旨在选择性感染、复制和裂解恶性细胞，而不会对正常健康组织造成伤害。除了直接溶瘤活性之外，OV还显示出作为免疫抑制剂的双重前景。病毒感染的存在和随后产生的免疫原性肿瘤细胞死亡触发介导进一步肿瘤破坏的先天性和适应性免疫应答。然而，抗病毒免疫应答可以内在地限制OV感染、传播和总体治疗功效。宿主免疫系统既可以作为屏障，也可以作为促进剂，有时根据病毒感染的阶段同时作为屏障和促进剂。因此，操纵宿主免疫系统以最小化抗病毒应答和病毒清除，同时仍然促进免疫介导的肿瘤破坏仍然是溶瘤病毒疗法面临的关键挑战。最近的临床试验已经确定了病毒疗法治疗各种恶性肿瘤的安全性、耐受性和有效性。最值得注意的是，talimogene laherparepvec（T-VEC），一种基因工程的表达粒细胞巨噬细胞集落刺激因子的溶瘤疱疹病毒，最近被批准用于治疗黑色素瘤，这是FDA批准的第一个OV作为美国的抗癌疗法。这篇综述讨论了OVs及其抗肿瘤特性，其与免疫系统的复杂相互作用，病毒疗法与现有癌症治疗之间的协同作用，以及增强OVs作为抗癌疗法的疗效的新兴策略。
Oncolytic viruses (OVs) are an emerging class of targeted anticancer therapies designed to selectively infect, replicate in, and lyse malignant cells without causing harm to normal, healthy tissues. In addition to direct oncolytic activity, OVs have shown dual promise as immunotherapeutic agents. The presence of viral infection and subsequently generated immunogenic tumor cell death trigger innate and adaptive immune responses that mediate further tumor destruction. However, antiviral immune responses can intrinsically limit OV infection, spread, and overall therapeutic efficacy. Host immune system can act both as a barrier as well as a facilitator and sometimes both at the same time based on the phase of viral infection. Thus, manipulating the host immune system to minimize antiviral responses and viral clearance while still promoting immune-mediated tumor destruction remains a key challenge facing oncolytic virotherapy. Recent clinical trials have established the safety, tolerability, and efficacy of virotherapies in the treatment of a variety of malignancies. Most notably, talimogene laherparepvec (T-VEC), a genetically engineered oncolytic herpesvirus-expressing granulocyte macrophage colony stimulating factor, was recently approved for the treatment of melanoma, representing the first OV to be approved by the FDA as an anticancer therapy in the US. This review discusses OVs and their antitumor properties, their complex interactions with the immune system, synergy between virotherapy and existing cancer treatments, and emerging strategies to augment the efficacy of OVs as anticancer therapies.