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溶瘤(复制型)腺病毒作为抗癌药物。

Oncolytic (replication-competent) adenoviruses as anticancer agents.

机构信息

Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, USA.

出版信息

Expert Opin Biol Ther. 2010 Mar;10(3):353-68. doi: 10.1517/14712590903559822.

Abstract

IMPORTANCE OF THE FIELD

Whilst therapies for neoplasies have advanced tremendously in the last few decades, there is still a need for new anti-cancer treatments. One option is genetically-engineered oncolytic adenovirus (Ad) 'vectors'. These kill cancer cells via the viral replication cycle, and amplify the anti-tumor effect by producing progeny virions able to infect neighboring tumor cells.

AREAS COVERED IN THIS REVIEW

We provide a description of basic Ad biology and summarize the literature for oncolytic Ads from 1996 to the present.

WHAT THE READER WILL GAIN

An overall view of oncolytic Ads, the merits and drawbacks of the various features of these vectors, and obstacles to further development and future directions for research.

TAKE HOME MESSAGE

Ads are attractive for gene therapy because they are relatively innocuous, easy to produce in large quantities, genetically stable, and easy to manipulate. A variety of have been constructed and tested, in pre-clinical and clinical experiments. Oncolytic Ads proved to be remarkably safe; no dose-limiting toxicity was observed in any clinical trial, and the maximum tolerated dose was not reached. At present, the major challenge for researchers is to increase the efficacy of the vectors, and to incorporate oncolytic virotherapy into existing treatment protocols.

摘要

重要性的领域

虽然肿瘤的治疗方法在过去几十年中取得了巨大的进展,但仍需要新的抗癌治疗方法。一种选择是基因工程的溶瘤腺病毒(Ad)“载体”。这些通过病毒复制周期杀死癌细胞,并通过产生能够感染邻近肿瘤细胞的子代病毒粒子来放大抗肿瘤效应。

这篇综述涵盖的领域

我们提供了基本 Ad 生物学的描述,并总结了 1996 年至今溶瘤 Ad 的文献。

读者将获得的收益

对溶瘤 Ad 的全面了解、这些载体的各种特征的优缺点,以及进一步发展的障碍和研究的未来方向。

需要注意的是

腺病毒因其相对无害、易于大量生产、遗传稳定和易于操作而成为基因治疗的理想选择。已经构建和测试了多种,包括在临床前和临床试验中。溶瘤 Ad 被证明是非常安全的;在任何临床试验中都没有观察到剂量限制毒性,也没有达到最大耐受剂量。目前,研究人员的主要挑战是提高载体的疗效,并将溶瘤病毒疗法纳入现有的治疗方案。

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