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 (C11R, K3L, and J2R) in various combinations, and their efficacy and safety were compared. The virus ultimately selected, named KLS-3010, exhibited strong antitumor activity against broad targets in vitro and in vivo. 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.

中文翻译：

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使用 IHD-W 菌株产生一种新型溶瘤痘苗病毒

溶瘤病毒因其选择性杀死肿瘤细胞和刺激宿主免疫系统的能力而成为有前景的癌症疗法。牛痘病毒作为溶瘤病毒平台，具有复制速度快、宿主靶点范围广、转基因掺入能力大等独特优势。在这项研究中，我们开发了一种新型溶瘤痘苗病毒，具有高效力和良好的安全性。我们从 International Health Department-White (IHD-W) 毒株开始，该毒株在所测试的四种牛痘病毒毒株中对肿瘤细胞具有最强的细胞毒性。接下来，通过删除三个病毒基因（C11R、K3L和J2R ）构建了几种候选病毒。) 在各种组合中，并比较了它们的疗效和安全性。最终选择的病毒命名为 KLS-3010，在体外和体内对广泛的靶标表现出很强的抗肿瘤活性。此外，KLS-3010 在小鼠中显示出良好的安全性，这由生物分布和体重变化决定。更有希望的是，KLS-3010 能够将肿瘤微环境转变为促炎状态，KLS-3010 给药后活化淋巴细胞的增加就证明了这一点，这表明该菌株可能引发溶瘤病毒介导的免疫反应。因此，KLS-3010 毒株代表了进一步开发基于溶瘤病毒的癌症疗法的有前景的平台。