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

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 trans...

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Main Authors:	Abschuetz, Oliver, Osen, Wolfram, Frank, Kathrin, Kato, Masashi, Schadendorf, Dirk, Umansky, Viktor
Format:	Online
Language:	English
Published:	MDPI 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712696/

id	pubmed-3712696
recordtype	oai_dc
spelling	pubmed-37126962013-08-05 T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma Abschuetz, Oliver Osen, Wolfram Frank, Kathrin Kato, Masashi Schadendorf, Dirk Umansky, Viktor Article 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. MDPI 2012-04-26 /pmc/articles/PMC3712696/ /pubmed/24213320 http://dx.doi.org/10.3390/cancers4020490 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Abschuetz, Oliver Osen, Wolfram Frank, Kathrin Kato, Masashi Schadendorf, Dirk Umansky, Viktor
spellingShingle	Abschuetz, Oliver Osen, Wolfram Frank, Kathrin Kato, Masashi Schadendorf, Dirk Umansky, Viktor T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
author_facet	Abschuetz, Oliver Osen, Wolfram Frank, Kathrin Kato, Masashi Schadendorf, Dirk Umansky, Viktor
author_sort	Abschuetz, Oliver
title	T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
title_short	T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
title_full	T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
title_fullStr	T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
title_full_unstemmed	T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma
title_sort	t-cell mediated immune responses induced in ret transgenic mouse model of malignant melanoma
description	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.
publisher	MDPI
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712696/
_version_	1611995197414047744

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

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