Oncolytic virotherapy.

Oncolytic virotherapy.
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DOI:
10.1038/nbt.2287
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发表时间:
2012-07-10
影响因子:
46.9
通讯作者:
--
中科院分区:
工程技术1区
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--
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溶瘤病毒疗法是一种新兴的治疗方式,其使用具有复制能力的病毒来破坏癌症。过去两年的进展包括单次注射病毒疗法治愈的可行性的临床前证明,加速肿瘤内病毒繁殖的药物的鉴定,最大化溶瘤病毒疗法的免疫潜力的新策略,以及血管递送和肿瘤内病毒复制的关键病毒血症阈值的临床确认。主要的临床里程碑是完成了一项III期试验中的招募,该试验是使用拉他莫基治疗转移性黑色素瘤的瘤内单纯疱疹病毒治疗。该领域面临的挑战是从数量不断增加的溶瘤平台和工程衍生物中选择“赢家”,暂时抑制但随后释放免疫系统的力量,以最大限度地提高病毒传播和抗癌免疫力,开发更有意义的临床前病毒治疗模型,并制造产量比现有疫苗制造工艺高出几个数量级的病毒。
Oncolytic virotherapy is an emerging treatment modality which uses replication competent viruses to destroy cancers. Advances in the past two years include preclinical proof of feasibility for a single-shot virotherapy cure, identification of drugs that accelerate intratumoral virus propagation, new strategies to maximize the immunotherapeutic potential of oncolytic virotherapy, and clinical confirmation of a critical viremic thereshold for vascular delivery and intratumoral virus replication. The primary clinical milestone was completion of accrual in a phase III trial of intratumoral herpes simplex virus therapy using talimogene laherparepvec for metastatic melanoma. Challenges for the field are to select ‘winners’ from a burgeoning number of oncolytic platforms and engineered derivatives, to transiently suppress but then unleash the power of the immune system to maximize both virus spread and anticancer immunity, to develop more meaningful preclinical virotherapy models and to manufacture viruses with orders of magnitude higher yields compared to established vaccine manufacturing processes.
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