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Updated: Aug 29, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Immunotherapeutic targeting of shared melanoma-associated antigens in a murine glioma model
Robert M Prins1, Sylvia K Odesa, Linda M Liau
1Department of Surgery/Neurosurgery, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095-6901, USA.
Abstract:
Immune-based treatments for central nervous system gliomas have traditionally lagged behind those of more immunogenic tumors such as melanoma. The relative paucity of defined glioma-associated antigens that can be targeted by the immune system may partially account for this situation. Antigens present on melanomas have been extensively characterized, both in humans and in murine preclinical models. Melanocytes and astrocytes are both derived embryologically from the neural ectoderm. Their neoplastic counterparts, malignant melanomas and gliomas, have been shown in humans to share common antigens at the RNA level. However, little is known concerning whether gliomas can be targeted by immune-based strategies that prime T cells to epitopes from melanoma-associated antigens (MAAs). In this study, we provide evidence that two common murine glioma cell lines (GL26 and GL261) express the melanoma antigens gp100 and tyrosinase-related protein 2 (TRP-2). To understand the immunogenicity of murine gliomas to CD8(+) T cells, we examined the ability of a MAA-specific CTL cell line to lyse the glioma cells, as well as the in vivo expansion of MAA-specific CD8(+) T cells in animals harboring gliomas. Both glioma cell lines were lysed by a human gp100-specific CTL cell line in vitro. Mice harboring s.c. GL26 gliomas possessed TRP-2-specific CD8(+) T cells, providing further evidence that these gliomas express the protein products in the context of MHC class I. Furthermore, MAA peptide-pulsed dendritic cells could prime T cells that specifically recognize GL26 glioma cells in vitro. Lastly, mice that were prevaccinated with human gp100 and TRP-2 peptide-pulsed dendritic cells had significantly extended survival when challenged with tumor cells in the brain, resulting in >50% long-term survival. These results suggest that shared MAAs on gliomas can be targeted immunotherapeutically, pointing the way to a new potential treatment option for patients with malignant gliomas.
Insights
Gliomas can be targeted using melanoma-associated antigens (MAAs) to prime immune cells. This approach significantly extended survival in mice with brain tumors, suggesting a new immunotherapy option for glioma patients.
Area of Science:
- Immunology
- Neuro-oncology
- Cancer immunotherapy
Background:
- Immune-based treatments for gliomas are less advanced than for other cancers like melanoma.
- Gliomas express fewer known tumor-associated antigens compared to melanomas.
- Melanoma-associated antigens (MAAs) are well-characterized and present on melanomas.
Purpose of the Study:
- To investigate if gliomas can be targeted by immune strategies using melanoma-associated antigens (MAAs).
- To determine if murine glioma cell lines express common MAAs.
- To assess the immunogenicity of gliomas to CD8(+) T cells and the potential for immunotherapy.
Main Methods:
- Murine glioma cell lines (GL26, GL261) were tested for expression of MAAs gp100 and tyrosinase-related protein 2 (TRP-2).
- MAA-specific cytotoxic T lymphocyte (CTL) activity against glioma cells was evaluated in vitro.
- In vivo expansion of MAA-specific CD8(+) T cells in tumor-bearing mice was assessed.
- Dendritic cells pulsed with MAA peptides were used to prime T cells and vaccinate mice.
Main Results:
- GL26 and GL261 glioma cells expressed gp100 and TRP-2.
- MAA-specific CTLs lysed glioma cells in vitro.
- MAA peptide-pulsed dendritic cells primed T cells that recognized GL26 glioma cells.
- Mice vaccinated with MAA peptide-pulsed dendritic cells showed significantly extended survival (>50% long-term survival).
Conclusions:
- Gliomas express melanoma-associated antigens (MAAs) that can be recognized by the immune system.
- Targeting shared MAAs on gliomas with immunotherapy is a viable strategy.
- This approach offers a potential new treatment avenue for malignant gliomas.
