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Cancers 2012, 4(2), 490-503; doi:10.3390/cancers4020490
Article

T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

1,†, 2,†, 1, 3, 4 and 1,*
Received: 27 February 2012; in revised form: 4 April 2012 / Accepted: 18 April 2012 / Published: 26 April 2012
(This article belongs to the Special Issue Tumor Stroma)
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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.
Keywords: melanoma; transgenic mouse model; T cells; immunization, cytokines; melanoma associated antigens melanoma; transgenic mouse model; T cells; immunization, cytokines; melanoma associated antigens
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Abschuetz, O.; Osen, W.; Frank, K.; Kato, M.; Schadendorf, D.; Umansky, V. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma. Cancers 2012, 4, 490-503.

AMA Style

Abschuetz O, Osen W, Frank K, Kato M, Schadendorf D, Umansky V. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma. Cancers. 2012; 4(2):490-503.

Chicago/Turabian Style

Abschuetz, Oliver; Osen, Wolfram; Frank, Kathrin; Kato, Masashi; Schadendorf, Dirk; Umansky, Viktor. 2012. "T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma." Cancers 4, no. 2: 490-503.



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