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基因工程痘苗病毒作为癌症治疗、成像及转基因递送的载体

Genetically Engineered Vaccinia Viruses As Agents for Cancer Treatment, Imaging, and Transgene Delivery.

作者信息

Haddad Dana

机构信息

Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

出版信息

Front Oncol. 2017 May 23;7:96. doi: 10.3389/fonc.2017.00096. eCollection 2017.

Abstract

Despite advances in technology, the formidable challenge of treating cancer, especially if advanced, still remains with no significant improvement in survival rates, even with the most common forms of cancer. Oncolytic viral therapies have shown great promise for the treatment of various cancers, with the possible advantages of stronger treatment efficacy compared to conventional therapy due to higher tumor selectivity, and less toxicity. They are able to preferentially and selectively propagate in cancer cells, consequently destroying tumor tissue mainly cell lysis, while leaving non-cancerous tissues unharmed. Several wild-type and genetically engineered vaccinia virus (VACV) strains have been tested in both preclinical and clinical trials with promising results. Greater understanding and advancements in molecular biology have enabled the generation of genetically engineered oncolytic viruses for safer and more efficacious treatment, including arming VACVs with cytokines and immunostimulatory molecules, anti-angiogenic agents, and enzyme prodrug therapy, in addition to combining VACVs with conventional external and systemic radiotherapy, chemotherapy, immunotherapy, and other virus strains. Furthermore, novel oncolytic vaccinia virus strains have been generated that express reporter genes for the tracking and imaging of viral therapy and monitoring of therapeutic response. Further study is needed to unlock VACVs' full potential as part of the future of cancer therapy.

摘要

尽管技术取得了进步,但治疗癌症,尤其是晚期癌症,仍然面临巨大挑战,即使是最常见的癌症类型,生存率也没有显著提高。溶瘤病毒疗法在治疗各种癌症方面显示出巨大潜力,与传统疗法相比,它可能具有更强的治疗效果,原因在于其对肿瘤的选择性更高,毒性更小。它们能够在癌细胞中优先且选择性地繁殖,从而主要通过细胞裂解破坏肿瘤组织,同时使非癌组织不受损害。几种野生型和基因工程痘苗病毒(VACV)毒株已在临床前和临床试验中进行了测试,结果令人鼓舞。分子生物学方面更深入的理解和进展使得基因工程溶瘤病毒得以产生,用于更安全、更有效的治疗,包括为VACV配备细胞因子和免疫刺激分子、抗血管生成剂以及酶前药疗法,此外还将VACV与传统的外部和全身放疗、化疗、免疫疗法以及其他病毒毒株相结合。此外,已经产生了新型溶瘤痘苗病毒毒株,这些毒株表达报告基因,用于病毒治疗的追踪和成像以及治疗反应的监测。作为癌症治疗未来的一部分,需要进一步研究以释放VACV的全部潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ba52/5440573/a30a189e02ac/fonc-07-00096-g001.jpg

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