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.
<p>Supplementary Figure 1. Immune-edited CaSki P3 cells showed a stem-like phenotype. Supplementary Figure 2. NANOG does not effect on acetylation of histone H4. Supplementary Figure 3. Expression of HDAC genes, and genes involved in negative regulators of MCL-1 protein by NANOG-HDAC1 axis. Supplementary Figure 4. The NANOG-HDAC1 axis controls immune-resistance, drug-resistance and stem-like property in multiple types of human cancer cells. Supplementary Figure 5. Generation of MDA-MB231 P3 immune-resistant cell lines. Supplementary Figure 6. Regulation of HAT genes by NANOG-HDAC1 axis. Supplementary Figure 7. Schematic interpretation of immune selection-mediated epigenetic change and implications of epigenetic therapy.</p>
<p>Supplementary Figure 1. Immune-edited CaSki P3 cells showed a stem-like phenotype. Supplementary Figure 2. NANOG does not effect on acetylation of histone H4. Supplementary Figure 3. Expression of HDAC genes, and genes involved in negative regulators of MCL-1 protein by NANOG-HDAC1 axis. Supplementary Figure 4. The NANOG-HDAC1 axis controls immune-resistance, drug-resistance and stem-like property in multiple types of human cancer cells. Supplementary Figure 5. Generation of MDA-MB231 P3 immune-resistant cell lines. Supplementary Figure 6. Regulation of HAT genes by NANOG-HDAC1 axis. Supplementary Figure 7. Schematic interpretation of immune selection-mediated epigenetic change and implications of epigenetic therapy.</p>
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