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Published on: November 24, 2014
Oncolytic therapy using a mutant type-1 herpes simplex virus and the role of the immune system
E S Lambright1, D J Caparrelli, A E Abbas
1Harrison Department of Surgical Research, University of Pennsylvania Medical Center, Philadelphia, USA.
Background:
Herpes simplex virus (HSV)-1716, a replication-restricted herpes simplex virus type 1, has shown efficacy as an oncolytic treatment for central nervous system tumors, breast cancer, ovarian cancer, and malignant mesothelioma. We evaluated the efficacy of HSV-1716 in a murine lung cancer model, Lewis lung carcinoma.
Methods:
Lewis lung carcinoma cells were infected with HSV-1716 and implanted in the flanks of mice at varying ratios of infected to uninfected cells. Tumor burden was assessed by measurement of the weight of the tumor nodule. The role of the immune system was examined by performing experiments in both immunocompetent and SCID mice. Tumors were implanted in the opposite flank to evaluate the vaccine effect.
Results:
In immunocompetent and SCID animals, ratio of 1:10 (infected-to-uninfected) cells completely prevented tumor formation and ratio of 1:100 suppressed tumor growth. Established tumors at a distant site in the groups receiving HSV-1716 infected cells showed no difference in size versus control, suggesting absence of a vaccine effect.
Conclusions:
We conclude that HSV-1716 may provide a oncolytic therapy for lung cancer even in the absence of immune system induction and a "carrier" cell could potentially deliver this vector.
Insights
Herpes simplex virus (HSV)-1716 effectively prevented or suppressed Lewis lung carcinoma growth in mice. This oncolytic therapy shows promise for lung cancer treatment, even without immune system involvement.
Area of Science:
- Oncolytic virotherapy
- Cancer research
- Immunology
Background:
- Herpes simplex virus (HSV)-1716 is a replication-restricted HSV-1 with demonstrated efficacy against various cancers.
- Previous studies highlight its potential in treating central nervous system tumors, breast cancer, ovarian cancer, and malignant mesothelioma.
Purpose of the Study:
- To evaluate the efficacy of HSV-1716 as an oncolytic therapy in a murine model of lung cancer, specifically Lewis lung carcinoma.
- To investigate the role of the immune system in HSV-1716's oncolytic activity.
Main Methods:
- Lewis lung carcinoma cells were infected with HSV-1716 and implanted in mice at varying ratios of infected to uninfected cells.
- Tumor burden was quantified by measuring tumor nodule weight.
- Experiments were conducted in both immunocompetent and severe combined immunodeficient (SCID) mice to assess the immune system's role.
- A vaccine effect was evaluated by implanting tumors on the opposite flank.
Main Results:
- A 1:10 ratio of infected-to-uninfected cells completely prevented tumor formation in both immunocompetent and SCID mice.
- A 1:100 ratio significantly suppressed tumor growth.
- No significant difference in tumor size was observed in distant sites, indicating no vaccine effect.
Conclusions:
- HSV-1716 demonstrates potential as an oncolytic therapy for lung cancer, independent of immune system induction.
- The findings suggest that a "carrier" cell could be utilized to deliver HSV-1716 for therapeutic purposes.
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