Related Experiment Video
Updated: Feb 26, 2026
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Stem cell-released oncolytic herpes simplex virus has therapeutic efficacy in brain metastatic melanomas
Wanlu Du1, Ivan Seah1, Oumaima Bougazzoul1
1Center for Stem Cell Therapeutics and Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114.
Abstract:
The recent Food and Drug Administration approval of immunogenic oncolytic virus (OV) has opened a new era in the treatment of advanced melanoma; however, approximately 50% of patients with melanoma develop brain metastasis, and currently there are no beneficial treatment options for such patients. To model the progression of metastases seen in patients and to overcome the hurdles of systemic delivery of OV, we developed melanoma brain metastasis models in immunocompromised and immunocompetent mice, and tested the fate and efficacy of oncolytic herpes simplex virus (oHSV)-armed mesenchymal stem cells (MSCs). Using brain-seeking patient-derived melanoma cells and real-time in vivo imaging, we show a widespread distribution of micrometastases and macrometastases in the brain, recapitulating the progression of multifoci metastases seen in patients. We armed MSCs with different oHSV variants (MSC-oHSV) and found that intracarotid administration of MSC-oHSV, but not of purified oHSV alone, effectively tracks metastatic tumor lesions and significantly prolongs the survival of brain tumor-bearing mice. In a syngeneic model of melanoma brain metastasis, a combination of MSC-oHSV and PD-L1 blockade increases IFNγ-producing CD8+ tumor-infiltrating T lymphocytes and results in a profound extension of the median survival of treated animals. This study thus demonstrates the utility of MSCs as OV carriers to disseminated brain lesions, and provides a clinically applicable therapeutic platform to target melanoma brain metastasis.
Insights
Mesenchymal stem cells (MSCs) carrying oncolytic herpes simplex virus (oHSV) effectively target melanoma brain metastases. This novel therapy significantly improves survival in preclinical models, offering a promising new treatment strategy.
Area of Science:
- Oncology
- Virology
- Immunology
- Neuroscience
Background:
- Advanced melanoma frequently metastasizes to the brain, with limited effective treatment options.
- Oncolytic viruses (OVs) show promise but face challenges in systemic delivery for brain metastases.
- Melanoma brain metastasis models are crucial for developing and testing new therapies.
Purpose of the Study:
- To develop and evaluate mesenchymal stem cell-armed oncolytic herpes simplex virus (MSC-oHSV) for treating melanoma brain metastases.
- To model the progression of multifocal brain metastases in immunocompromised and immunocompetent mice.
- To assess the efficacy of MSC-oHSV, alone and in combination with PD-L1 blockade, in preclinical melanoma brain metastasis models.
Main Methods:
- Development of brain-seeking patient-derived melanoma cell lines.
- Establishment of immunocompromised and syngeneic mouse models of melanoma brain metastasis.
- Intracarotid administration of MSC-oHSV and assessment of tumor targeting and survival.
- Combination therapy with MSC-oHSV and PD-L1 blockade, evaluating immune responses.
Main Results:
- MSC-oHSV effectively tracked and targeted widespread melanoma micrometastases and macrometastases in the brain.
- Intracarotid MSC-oHSV administration significantly prolonged survival in brain tumor-bearing mice compared to purified oHSV.
- Combination therapy of MSC-oHSV and PD-L1 blockade enhanced CD8+ T cell responses and profoundly extended median survival.
Conclusions:
- Mesenchymal stem cells serve as effective carriers for oncolytic viruses targeting disseminated brain lesions.
- MSC-oHSV represents a clinically applicable therapeutic platform for melanoma brain metastasis.
- This approach holds significant potential for improving outcomes in patients with advanced melanoma and brain metastases.
