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病毒纳米颗粒:癌症疫苗与免疫调节剂

Viral Nanoparticles: Cancer Vaccines and Immune Modulators.

作者信息

Fusciello Manlio, Ylösmäki Erkko, Cerullo Vincenzo

机构信息

Drug Research Program, Division of Pharmaceutical Biosciences and Digital Precision Cancer Medicine Flagship (iCAN), Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

Department of Molecular Medicine and Medical Biotechnology and CEINGE, Naples University Federico II, Naples, Italy.

出版信息

Adv Exp Med Biol. 2021;1295:317-325. doi: 10.1007/978-3-030-58174-9_14.

Abstract

In the last decades, viruses have gained great interest in the field of immuno-oncology (I-O) for their ability of interacting both with the immune system and the tumour microenvironment. Those pathogens have naturally evolved and been evolutionary to specifically infect hosts, replicate, deliver their genome, and spread. These properties, initially considered a disadvantage, have been investigated and edited to turn viruses into precious allies for molecular biology serving as gene therapy vectors, adjuvants for the immune system, drug cargos, and, lately, anticancer therapeutics. As anticancer drug, one interesting option is viral engineering. Modification of either the viral genome or the outer shell of viruses can change infectivity and tissue targeting and add new functions to the viral particle. Remarkably, in the field of cancer virotherapy, scientists realized that a specific viral genomic depletion would turn the normal tropism of viruses to conditionally replicate in cancer cells only. This category of viruses, named 'Oncolytic viruses', have been investigated and used for cancer treatment in the past decades resulting in the approval of the first oncolytic virus, a herpes simplex virus expressing a stimulating factor, named T-Vec, in 2015. As such, oncolytic viruses achieved positive outcome but still are not able to completely eradicate the disease. This has brought the scientific community to edit those agents, adding to their ability to directly lysate cancer cells, few modifications to mainly boost their interaction with the immune system. Viruses experienced then a renaissance not only as infecting agent but as nanoparticle and cancer vaccines too. These strategies bring new life to the concept of using viruses as viral particles for therapeutic applications.

摘要

在过去几十年中,病毒因其与免疫系统和肿瘤微环境相互作用的能力而在免疫肿瘤学(I-O)领域引起了极大关注。这些病原体自然进化并具有特异性感染宿主、复制、传递其基因组和传播的能力。这些特性最初被认为是一种劣势,但现在已被研究和编辑,以使病毒成为分子生物学的宝贵盟友,用作基因治疗载体、免疫系统佐剂、药物载体,以及最近的抗癌治疗剂。作为抗癌药物,一个有趣的选择是病毒工程。对病毒基因组或病毒外壳进行修饰可以改变感染性和组织靶向性,并为病毒颗粒添加新功能。值得注意的是,在癌症病毒治疗领域,科学家们意识到特定的病毒基因组缺失会使病毒的正常嗜性转变为仅在癌细胞中有条件地复制。这类病毒被称为“溶瘤病毒”,在过去几十年中已被研究并用于癌症治疗,2015年第一种溶瘤病毒——一种表达刺激因子的单纯疱疹病毒,名为T-Vec——获得批准。因此,溶瘤病毒取得了积极的成果,但仍无法完全根除疾病。这促使科学界对这些药物进行编辑,除了增强它们直接裂解癌细胞的能力外,还进行了一些修饰以主要增强它们与免疫系统的相互作用。病毒不仅作为感染因子,而且作为纳米颗粒和癌症疫苗经历了复兴。这些策略为将病毒用作治疗应用的病毒颗粒这一概念带来了新的生机。

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