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Updated: May 6, 2026
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
Oliver Abschuetz1, Wolfram Osen, Kathrin Frank
1Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120, Germany. v.umansky@dkfz.de.
Abstract:
Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.
Insights
A novel transgenic mouse model spontaneously develops melanoma, mimicking human disease. This model shows promise for evaluating new melanoma immunotherapies by assessing T cell responses against melanoma-associated antigens.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Human malignant melanoma exhibits poor response to current treatments, necessitating innovative therapeutic strategies.
- Effective evaluation of new therapies requires animal models that accurately recapitulate human melanoma's genetic, histopathological, and clinical characteristics.
Purpose of the Study:
- To develop and characterize a transgenic mouse model for spontaneous skin melanoma.
- To assess the utility of this model for preclinical evaluation of melanoma immunotherapies.
Main Methods:
- Utilized a transgenic mouse model with ret transgene expression in melanocytes under a metallothionein-I promoter.
- Analyzed tumor development, metastasis, expression of melanoma-associated antigens (MAAs), and T cell responses following peptide vaccination.
Main Results:
- Approximately 25% of mice developed macroscopic skin melanoma with distant metastases; others had metastatic lesions without visible skin tumors.
- Tumor lesions expressed key MAAs: tyrosinase, TRP-1, TRP-2, and gp100.
- Mice without macroscopic tumors generated T cell responses against MAA TRP-2 upon vaccination, while tumor-bearing mice showed significantly down-regulated T cell reactivity.
Conclusions:
- The ret transgenic mouse model effectively mimics spontaneous melanoma with metastatic potential.
- This model is suitable for preclinical assessment of novel melanoma immunotherapies targeting MAAs.
- The model allows for the study of immune responses in the context of melanoma development and progression.
