Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma
- Title
- Efficacy of combining ING4 and TRAIL genes in cancer-targeting gene virotherapy strategy: first evidence in preclinical hepatocellular carcinoma
- Author
- 윤채옥
- Keywords
- NF-KAPPA-B; TUMOR-GROWTH; APOPTOSIS; THERAPY; INHIBITOR; CELLS; ANGIOGENESIS; EXPRESSION; ANTIANGIOGENESIS; INTERLEUKIN-12
- Issue Date
- 2018-01
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- GENE THERAPY, v. 25, no. 1, page. 54-65
- Abstract
- Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono-and combined therapy with OAds armed with ING4 (Ad-Delta B/ING4) and TRAIL (Ad-Delta B/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-Delta B/TRAIL and/or Ad-Delta B/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-Delta B/ING4 plus Ad-Delta B/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-Delta B/ING4 and Ad-Delta B/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-Delta B/ING4 and Ad-Delta B/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.
- URI
- https://www.nature.com/articles/gt201786https://repository.hanyang.ac.kr/handle/20.500.11754/117019
- ISSN
- 0969-7128; 1476-5462
- DOI
- 10.1038/gt.2017.86
- Appears in Collections:
- COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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