Recombinant Poliovirus for Cancer Immunotherapy.
Recombinant Poliovirus for Cancer Immunotherapy.
复制标题
重组脊髓灰质炎病毒用于癌症免疫疗法。
DOI：
10.1146/annurev-med-050715-104655
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发表时间：
2018-01-29
影响因子：
10.5
通讯作者：
Nair SK
中科院分区：
文献类型：
--
作者：
Gromeier M;Nair SK
引发抗病毒免疫的机制，即宿主对病毒病原体攻击的自然反应，与癌症免疫治疗迫在眉睫。“溶瘤”病毒是自然存在的或基因工程病毒制剂，在恶性细胞中具有细胞类型特异性繁殖，表面上是由于其肿瘤细胞毒性而被设想的。然而，它们真正的治疗价值可能在于它们能够激发抗病毒信号，在免疫抑制的肿瘤微环境中参与抗肿瘤免疫反应。选择这种“溶瘤”病毒制剂来激发抗肿瘤免疫并不是一件容易的事。在与宿主的共同进化过程中，病毒获得了复杂的策略来阻断炎症信号，拦截先天抗病毒干扰素反应和阻止抗病毒效应反应，例如通过干扰抗原呈递和T细胞共刺激。由此产生的宿主先天炎症和抗病毒反应与病毒免疫逃避和抑制的斗争，决定了抗肿瘤免疫发生的潜力。此外，在正常免疫活性生物中建立的早期宿主：病毒关系的范例可能不适用于免疫抑制的肿瘤微环境。在这篇综述中，我们解释了重组非致病性脊髓灰质炎病毒PVSRIPO的机制，该病毒目前正处于治疗复发性胶质母细胞瘤的1期临床试验中。我们专注于一种不寻常的宿主：病毒关系，由脊髓灰质炎病毒的简单和细胞毒性复制策略定义，它产生有利于肿瘤抗原特异性免疫启动的炎症扰动。
Mechanisms to elicit antiviral immunity, a natural host response to viral pathogen challenge, are of imminent relevance to cancer immunotherapy. ‘Oncolytic’ viruses, naturally existing or genetically engineered viral agents with cell type-specific propagation in malignant cells, were ostensibly conceived for their tumor cytotoxic properties. Yet, their true therapeutic value may rest in their ability to provoke antiviral signals that engage antitumor immune responses within the immunosuppressive tumor microenvironment. Coopting such ‘oncolytic’ viral agents to instigate antitumor immunity is not an easy feat. During co-evolution with their hosts, viruses acquired sophisticated strategies to block inflammatory signals, intercept innate antiviral interferon responses and prevent antiviral effector responses, e.g. by interfering with antigen presentation and T cell costimulation. The resulting struggle of host innate inflammatory and antiviral responses vs. viral immune evasion and suppression, determines the potential for antitumor immunity to occur. Moreover, paradigms of early host:virus relations established in normal immunocompetent organisms may not hold in the profoundly immunosuppressive tumor microenvironment. In this review, we explain the mechanisms of recombinant non-pathogenic poliovirus, PVSRIPO, which is currently in Phase-1 clinical trials against recurrent glioblastoma. We focus on an unusual host:virus relationship, defined by the simple and cytotoxic replication strategy of poliovirus, which generates inflammatory perturbations conducive to tumor antigen-specific immune priming.
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DOI：
10.1038/mt.2008.184
发表时间：
2008-11
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
--
作者：
Dobrikova EY;Broadt T;Poiley-Nelson J;Yang X;Soman G;Giardina S;Harris R;Gromeier M
通讯作者：
Gromeier M
影响因子：
5.4
作者：
Brown, Michael C.;Dobrikov, Mikhail I.;Gromeier, Matthias
通讯作者：
Gromeier, Matthias
影响因子：
3.8
作者：
Freistadt, MS;Eberle, KE
通讯作者：
Eberle, KE
影响因子：
5.4
作者：
Brown, Michael C.;Bryant, Jeffrey D.;Gromeier, Matthias
通讯作者：
Gromeier, Matthias
DOI：
10.1073/pnas.0900153106
发表时间：
2009-06-09
影响因子：
11.1
作者：
de Breyne, Sylvain;Yu, Yingpu;Hellen, Christopher U. T.
通讯作者：
Hellen, Christopher U. T.