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Treatment of experimental intracranial murine melanoma with a neuroattenuated herpes simplex virus 1 mutant
B P Randazzo1, S Kesari, R M Gesser
1Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Abstract:
Brain metastases occur commonly in the setting of a variety of human cancers. At present, such cases are invariably fatal and highlight a need for research on new therapies. We have developed a mouse brain tumor model utilizing the Harding-Passey melanoma cell line injected intracranially into C57Bl/6 mice. Tumors develop in 100% of the mice and can be detected by magnetic resonance imaging as early as 5 days post cell injection. Death from tumor progression occurs between 12 and 16 days post cell injection. Stereotactic injection of the neuroattenuated HSV-1 strain 1716 into brain tumors 5 or 10 days postinjection of the melanoma cells results in a statistically significant increase in the time to development of neurological symptoms and in complete tumor regression and the long-term survival of some treated animals. Moreover, viral titration studies and immunohistochemistry suggest that replication of this virus is restricted to tumor cells and does not occur in the surrounding brain tissue. These results suggest that HSV-1 mutant 1716 shows particular promise for use as a therapeutic agent for the treatment of brain tumors.
Insights
A novel mouse model for brain tumors showed that a modified herpes simplex virus (HSV-1) can effectively target and reduce tumors. This offers promising new therapeutic strategies for brain cancer treatment.
Area of Science:
- Oncology
- Virology
- Neuroscience
Background:
- Brain metastases are a common and fatal complication of various cancers.
- Current treatment options for brain tumors are limited, necessitating novel therapeutic approaches.
- A reliable animal model is crucial for preclinical evaluation of new brain tumor therapies.
Purpose of the Study:
- To develop and characterize a preclinical mouse model for brain tumors.
- To evaluate the therapeutic efficacy of a neuroattenuated herpes simplex virus type 1 (HSV-1) strain (1716) in this model.
- To assess the safety and tumor-targeting capabilities of HSV-1 1716.
Main Methods:
- Establishment of a brain tumor model by intracranial injection of Harding-Passey melanoma cells into C57Bl/6 mice.
- Tumor detection and monitoring using magnetic resonance imaging (MRI).
- Stereotactic administration of HSV-1 1716 into established brain tumors.
- Assessment of tumor regression, survival rates, and viral replication via titration and immunohistochemistry.
Main Results:
- The developed mouse model consistently produced brain tumors detectable by MRI within 5 days.
- Treatment with HSV-1 1716 significantly increased survival time and induced complete tumor regression in some animals.
- Viral replication was predominantly observed within tumor cells, with minimal spread to surrounding healthy brain tissue.
Conclusions:
- The Harding-Passey melanoma intracranial mouse model is a viable platform for brain tumor research.
- Neuroattenuated HSV-1 1716 demonstrates significant therapeutic potential against brain tumors.
- HSV-1 1716 exhibits tumor-selective replication, suggesting a favorable safety profile for brain tumor therapy.