Back to Search Start Over

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

Authors :
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
Source :
Human Gene Therapy, Hum Gene Ther
Publication Year :
2021
Publisher :
Mary Ann Liebert, Inc., publishers, 2021.

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 (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.

Details

Language :
English
ISSN :
15577422 and 10430342
Volume :
32
Issue :
9-10
Database :
OpenAIRE
Journal :
Human Gene Therapy
Accession number :
edsair.doi.dedup.....b354c62551099723dac91df0f206b212