Open AccessGeneration of a Novel Oncolytic Vaccinia Virus Using the IHD-W Strain
Author(s) -
Jaeil Shin,
Soon-Oh Hong,
Min-Ju Kim,
Hyesun Lee,
Hwanjun Choi,
Joonsung Kim,
Jong Ha Hong,
Hyesoo Kang,
Eun-Jin Lee,
Soondong Lee,
Byoungjae Kong,
Minjung Kim,
Hwanjun Choi,
Sujeong Kim
Publication year - 2021
Publication title -
human gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.633
H-Index - 149
eISSN - 1557-7422
pISSN - 1043-0342
DOI - 10.1089/hum.2020.050
Subject(s) - oncolytic virus , vaccinia , virus , virology , immune system , biology , orthopoxvirus , viral replication , poxviridae , cancer research , immunology , gene , genetics , recombinant dna
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.