Poor response of human malignant melanoma to currently available treatments\r\nrequires a development of innovative therapeutic strategies. Their evaluation should be\r\nbased on animal models that resemble human melanoma with respect to genetics,\r\nhistopathology and clinical features. Here we used a transgenic mouse model of\r\nspontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under\r\nthe control of metallothionein-I promoter. After a short latency, around 25% mice develop\r\nmacroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain,\r\nwhereas other transgenic mice showed only metastatic lesions without visible skin tumors.\r\nWe found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase,\r\ntyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for\r\nthe immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic\r\nmelanomas were able to generate T cell responses not only against a strong model antigen\r\novalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic\r\nprimary 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.\r\nWe suggest that ret transgenic mice could be used as a pre-clinical model for the\r\nevaluation of novel strategies of melanoma immunotherapy.
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