Background
Hepatocellular carcinoma (HCC) commonly presents at a late stage when surgery is no
longer a curative option. As such, novel therapies for advanced HCC are needed. Oncolytic
viruses are a viable option for cancer therapy owing to their ability to specifically
infect, replicate within, and kill cancer cells. In this study, we have investigated
the ability of GLV-2b372, a novel light-emitting recombinant vaccinia virus derived
from a wild-type Lister strain, to kill HCC.
Methods
Four human HCC cell lines were assayed in vitro for infectivity and cytotoxicity.
Viral replication was quantified via standard viral plaque assays. Flank HCC xenografts
generated in athymic nude mice were treated with intratumoral GLV-2b372 to assess
for tumor growth inhibition and viral biodistribution.
Results
Infectivity occurred in a time- and concentration-dependent manner with 70% cell death
in all cell lines by day 5. All cell lines supported efficient viral replication.
At 25 days after infection, flank tumor volumes decreased by 50% whereas controls
increased by 400%. Tumor tissue demonstrated substantial GLV-2b372 infection at 24 hours,
48 hours, and 2 weeks.
Conclusion
We demonstrate that GLV-2b372 efficiently kills human HCC in vitro and in vivo and
is a viable treatment option for patients with HCC.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Hepatocellular carcinoma from an immunologic perspective.Clin Cancer Res. 2013; 19: 6678-6685
- Global cancer statistics.CA Cancer J Clin. 2011; 61: 69-90
- Systemic therapies in hepatocellular carcinoma.Dig Dis. 2009; 27: 175-188
- A cancer-related protein 14-3-3zeta is a potential tumor-associated antigen in immunodiagnosis of hepatocellular carcinoma.Tumour Biol. 2014; 35: 4247-4256
- Oncolytic vaccinia virus for the treatment of cancer.Expert Opin Biol Ther. 2011; 11: 595-608
- Intravesical gene therapy: in vivo gene transfer using recombinant vaccinia virus vectors.Cancer Res. 1994; 54: 3325-3328
- Preferential replication of systemically delivered oncolytic vaccinia virus in focally irradiated glioma xenografts.Clin Cancer Res. 2012; 18: 2579-2590
- A novel recombinant vaccinia virus expressing the human norepinephrine transporter retains oncolytic potential and facilitates deep-tissue imaging.Mol Med. 2009; 15: 144-151
- Hepatocellular carcinoma: epidemiology and molecular carcinogenesis.Gastroenterology. 2007; 132: 2557-2576
- Extending survival with the use of targeted therapy in the treatment of hepatocellular carcinoma.Gastroenterol Hepatol. 2013; 9: 1-24
- The secret ally: immunostimulation by anticancer drugs.Nat Rev Drug Discov. 2012; 11: 215-233
- Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359: 378-390
- Systemic therapies in hepatocellular carcinoma: present and future.Future Oncol. 2013; 9: 1533-1548
- Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma.Hepatology. 2006; 44: 1465-1477
- Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus.J Transl Med. 2011; 9: 36
- The highly attenuated oncolytic recombinant vaccinia virus GLV-1h68: comparative genomic features and the contribution of F14.5L inactivation.Mol Genet Genomics. 2009; 282: 417-435
- Efficient colonization and therapy of human hepatocellular carcinoma (HCC) using the oncolytic vaccinia virus strain GLV-1h68.PLoS One. 2011; 6: e22069
Article info
Publication history
Published online: June 03, 2015
Accepted:
March 4,
2015
Footnotes
Supported in part by training grants T 32 CA09501 (J.C.), a grant for rare diseases research from “Cycle for Survival,” a grant from Mr. William H. and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research, and The Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center. The research grade virus production was supported by the Research and Development Division of Genelux Corporation.
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
