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利用 IHD-W 株生成新型溶瘤痘苗病毒。

Generation of a Novel Oncolytic Vaccinia Virus Using the IHD-W Strain.

机构信息

Institute of BioInnovation Research, Kolon Life Science, Seoul, Republic of Korea.

出版信息

Hum Gene Ther. 2021 May;32(9-10):517-527. doi: 10.1089/hum.2020.050. Epub 2020 Oct 15.

DOI:10.1089/hum.2020.050
PMID:32854548
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8140350/
Abstract

Oncolytic viruses are promising cancer therapies due to their selective killing of tumor cells and ability to stimulate the host immune system. As an oncolytic virus platform, vaccinia virus has unique advantages, including rapid replication, a broad range of host targets, and a large capacity for transgene incorporation. In this study, we developed a novel oncolytic vaccinia virus with high potency and a favorable safety profile. We began with the International Health Department-White (IHD-W) strain, which had the strongest cytotoxicity against tumor cells among the four vaccinia virus strains tested. Next, several candidate viruses were constructed by deleting three viral genes (, , and ) in various combinations, and their efficacy and safety were compared. The virus ultimately selected, named KLS-3010, exhibited strong antitumor activity against broad targets and . Furthermore, KLS-3010 showed a favorable safety profile in mice, as determined by the biodistribution and body weight change. More promisingly, KLS-3010 was able to shift the tumor microenvironment to a proinflammatory state, as evidenced by an increase in activated lymphocytes after KLS-3010 administration, suggesting that this strain may elicit an oncolytic virus-mediated immune response. The KLS-3010 strain thus represents a promising platform for the further development of oncolytic virus-based cancer therapies.

摘要

溶瘤病毒因其选择性杀伤肿瘤细胞和刺激宿主免疫系统的能力而成为有前途的癌症治疗方法。作为溶瘤病毒平台，痘苗病毒具有独特的优势，包括快速复制、广泛的宿主靶标和大容量的转基因整合。在这项研究中，我们开发了一种新型高效且具有良好安全性的溶瘤痘苗病毒。我们从国际卫生署-白（IHD-W）株开始，该株在四种痘苗病毒株中对肿瘤细胞的细胞毒性最强。接下来，通过以各种组合删除三个病毒基因（，和）构建了几种候选病毒，并比较了它们的功效和安全性。最终选择的病毒命名为 KLS-3010，对广泛的靶标和具有很强的抗肿瘤活性。此外，KLS-3010 在小鼠中的安全性良好，这可通过生物分布和体重变化来确定。更有前途的是，KLS-3010 能够将肿瘤微环境转变为促炎状态，这可通过 KLS-3010 给药后激活的淋巴细胞增加来证明，这表明该株可能引发溶瘤病毒介导的免疫反应。因此，KLS-3010 株代表了进一步开发溶瘤病毒癌症治疗的有前途的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/5aba491b4151/hum.2020.050_figure5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/086f506e125c/hum.2020.050_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/5bb5ed2ab093/hum.2020.050_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/72317c30fca9/hum.2020.050_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/6bf2b2e8cdb5/hum.2020.050_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/5aba491b4151/hum.2020.050_figure5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/086f506e125c/hum.2020.050_figure1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/5bb5ed2ab093/hum.2020.050_figure2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/72317c30fca9/hum.2020.050_figure3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/6bf2b2e8cdb5/hum.2020.050_figure4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0645/8140350/5aba491b4151/hum.2020.050_figure5.jpg

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