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Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats
Published on: April 15, 2016
Potent efficacy signals from systemically administered oncolytic herpes simplex virus (HSV1716) in hepatocellular
Lynne Braidwood1, Kirsty Learmonth1, Alex Graham1
1Virttu Biologics Ltd, Department of Neurology, Southern General Hospital, Glasgow, UK.
Abstract:
Oncolytic herpes simplex virus (HSV1716), lacking the neurovirulence factor ICP34.5, has highly selective replication competence for cancer cells and has been used in clinical studies of glioma, melanoma, head and neck squamous cell carcinoma, pediatric non-central nervous system solid tumors, and malignant pleural mesothelioma. To date, 88 patients have received HSV1716 and the virus is well tolerated, with selective replication in tumor cells and no spread to surrounding normal tissue. We assessed the potential value of HSV1716 in preclinical studies with two human hepatocellular carcinoma cell lines, HuH7 and HepG2-luc. HSV1716 displayed excellent replication kinetics in vitro in HepG2-luc cells, a cell line engineered to express luciferase, and virus-mediated cell killing correlated with loss of light emissions from the cells. In vivo, the HepG2-luc cells readily formed light-emitting xenografts that were easily visualized by an in vivo imaging system and efficiently eliminated by HSV1716 oncolysis after intratumoral injection. HSV1716 also demonstrated strong efficacy signals in subcutaneous HuH7 xenografts in nude mice after intravenous administration of virus. In the HuH7 model, the intravenously injected virus replicated prolifically immediately after efficient tumor localization, resulting in highly significant reductions in tumor growth and enhanced survival. Our preclinical results demonstrate excellent tumor uptake of HSV1716, with prolific replication and potent oncolysis. These observations warrant a clinical study of HSV1716 in hepatocellular carcinoma.
Insights
Oncolytic herpes simplex virus (HSV1716) shows promise for treating liver cancer. Preclinical studies demonstrate its ability to selectively target and destroy hepatocellular carcinoma cells, warranting further clinical investigation.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Oncolytic herpes simplex virus (HSV1716) is engineered to selectively replicate in cancer cells.
- Previous clinical studies have shown its safety and efficacy in various solid tumors.
Purpose of the Study:
- To evaluate the preclinical efficacy of HSV1716 against hepatocellular carcinoma (HCC).
- To assess HSV1716's replication, tumor targeting, and oncolytic potential in HCC models.
Main Methods:
- In vitro studies using human HCC cell lines (HuH7 and HepG2-luc).
- In vivo studies using HepG2-luc xenografts in mice for imaging and intratumoral injection.
- In vivo studies using HuH7 xenografts in mice for intravenous administration and efficacy assessment.
Main Results:
- HSV1716 demonstrated robust replication and potent oncolysis in vitro and in vivo.
- Intratumoral and intravenous administration of HSV1716 led to significant tumor growth reduction and enhanced survival in HCC xenograft models.
- The virus showed excellent tumor uptake and selective replication in tumor cells without spreading to normal tissues.
Conclusions:
- Preclinical data strongly support the potential of HSV1716 as a therapeutic agent for hepatocellular carcinoma.
- Further clinical studies of HSV1716 in HCC patients are warranted based on these promising results.
