溶瘤病毒疗法:问题与前景。

IF 6.7 Oncolytic Virotherapy Pub Date : 2013-05-31 eCollection Date: 2013-01-01 DOI:10.2147/OV.S39609
Laure Aurelian
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引用次数: 15

摘要

溶瘤病毒治疗是一种通过在快速增殖的细胞中选择性复制病毒来减轻肿瘤负担的新策略。溶瘤病毒是至少十个病毒科的成员,每个病毒科都有其优点和缺点。在这里,我简要回顾了最近的进展和主要挑战,以研究最好的平台为例。最近的进展包括可行性的临床前证明,耐受性和有效性的临床证据,以及提高疗效的新策略的发展。这些包括工程肿瘤选择性和抗肿瘤基因的表达,这些基因可以独立于病毒复制发挥作用,确定加速肿瘤内病毒传播的组合疗法,以及用于治疗转移性疾病的免疫反应和血管输送的修饰。关键的挑战是从不同的溶瘤平台中选择“赢家”,这些平台可以在不影响病毒复制的情况下刺激抗癌免疫,并可以溶解癌症干细胞,而癌症干细胞最有可能负责肿瘤的维持、侵袭性和复发。在病毒治疗过程中,通过激活多种死亡途径来防止耐药肿瘤细胞的出现,更好地了解癌症干细胞裂解的机制,以及开发更有意义的临床前动物模型,这些都是下一代工程病毒面临的额外挑战。
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Oncolytic virotherapy: the questions and the promise.

Oncolytic virotherapy is a new strategy to reduce tumor burden through selective virus replication in rapidly proliferating cells. Oncolytic viruses are members of at least ten virus families, each with its advantages and disadvantages. Here, I briefly review the recent advances and key challenges, as exemplified by the best-studied platforms. Recent advances include preclinical proof of feasibility, clinical evidence of tolerability and effectiveness, and the development of new strategies to improve efficacy. These include engineered tumor selectivity and expression of antitumorigenic genes that could function independently of virus replication, identification of combinatorial therapies that accelerate intratumoral virus propagation, and modification of immune responses and vascular delivery for treatment of metastatic disease. Key challenges are to select "winners" from the distinct oncolytic platforms that can stimulate anti-cancer immunity without affecting virus replication and can lyse cancer stem cells, which are most likely responsible for tumor maintenance, aggressiveness, and recurrence. Preventing the emergence of resistant tumor cells during virotherapy through the activation of multiple death pathways, the development of a better understanding of the mechanisms of cancer stem-cell lysis, and the development of more meaningful preclinical animal models are additional challenges for the next-generation of engineered viruses.

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