Generation of a Novel Oncolytic Vaccinia Virus Using the IHD-W Strain
| Autor: | Jae Il Shin, Lee Hyesun, Eunjin Lee, Min Jung Kim, Heonsik Choi, Hyesoo Kang, Min Ju Kim, Soon-Oh Hong, Hong Jieun, Byoungjae Kong, Sujeong Kim, Kim Joonsung, Lee Soondong, Hwanjun Choi |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
viruses
Vaccinia virus Biology Global Health Virus Replication Virus Proinflammatory cytokine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system In vivo Cell Line Tumor IHD-W strain Genetics Animals Tissue Distribution Cytotoxicity Molecular Biology vaccinia Research Articles 030304 developmental biology oncolytic virus Oncolytic Virotherapy 0303 health sciences Tumor microenvironment Correction Virology Oncolytic virus Oncolytic Viruses chemistry 030220 oncology & carcinogenesis Molecular Medicine Vaccinia |
| Zdroj: | Human Gene Therapy Hum Gene Ther |
| ISSN: | 1557-7422 1043-0342 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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