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Updated: Jul 29, 2026
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Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes
Published on: November 11, 2016
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Gene-edited and -engineered stem cell platform drives immunotherapy for brain metastatic melanomas
Nobuhiko Kanaya1,2, Yohei Kitamura1,2, Maria Lopez Vazquez1,2
1Center for Stem Cell and Translational Immunotherapy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Science Translational Medicine
|May 31, 2023
Summary
A novel twin stem cell (TSC) system delivers oncolytic herpes simplex virus (oHSV) and immune boosters to combat melanoma brain metastases. This immunotherapy strategy shows promise for treating challenging central nervous system (CNS) cancers.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cancer Metastasis
Background:
- Oncolytic virus therapy faces challenges in treating melanoma brain metastases due to delivery issues and tumor immunosuppression.
- PTEN-deficient melanoma brain metastasis models exhibit increased immunosuppression, mimicking clinical conditions.
Purpose of the Study:
- To develop and evaluate an allogeneic twin stem cell (TSC) system for enhanced oncolytic virus therapy in melanoma brain metastases.
- To overcome the immunosuppressive tumor microenvironment in the brain for improved therapeutic efficacy.
Main Methods:
- Established PTEN-deficient melanoma brain metastasis mouse models.
- Developed a twin stem cell (TSC) system with one population loaded with oncolytic herpes simplex virus (oHSV) and another gene-edited for oHSV resistance and immunomodulator release (GM-CSF).
- Utilized CRISPR-Cas9 gene editing to create Nectin-1 knockout (N1^KO) stem cells.
Main Results:
- Locoregional delivery of TSCs (TSC-G) activated dendritic cell and T cell immune responses in melanoma brain metastasis models.
- The TSC strategy demonstrated superior therapeutic efficacy compared to existing oncolytic viral therapies.
- A combination therapy (TSC-G/P) including anti-PD-1 showed efficacy in leptomeningeal metastasis models, including patient-derived ones.
Conclusions:
- The allogeneic SC-based immunotherapy strategy is a promising approach for treating melanomas in the central nervous system (CNS).
- This study provides a potential roadmap for the clinical translation of advanced oncolytic virus and cell-based immunotherapies for brain metastases.
