Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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SHR Neuro Krebs Kardio Lipid Stoffw Microb
Sorensen, RB; Junker, N; Kirkin, A; Voigt, H; Svane, IM; Becker, JC; Straten, PT; Andersen, MH.
The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the surface of many melanoma cell lines.
Cancer Immunol Immunother. 2009; 58(5):665-675
Doi: 10.1007/s00262-008-0588-0
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- Co-Autor*innen der Med Uni Graz
- Becker Jürgen Christian
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- Abstract:
- Among the relatively large number of known tumor-associated antigens (TAA) which are recognized by human CD8 T-cells, Melan-A/MART-1 is one of the most-if not the most-frequently used target for anti-cancer vaccines in HLA-A2 + melanoma patients. In this study, we analyzed the killing of a large panel of melanoma cells by a high avidity, MART-1-specific T-cell clone or a MART-1-specific, polyclonal T-cell culture. Strikingly, we observed that the MART-1-specific T-cells only killed around half of the analyzed melanoma cell lines. In contrast a Bcl-2-specific T-cell clone killed all melanoma cell lines, although the T-cell avidity of this clone was significantly lower. The MART-1-specific T-cell clone expressed NKG-2D and was fully capable of releasing both perforin and Granzyme B. Notably, the resistance to killing by the MART-1-specific T-cells could be overcome by pulsing of the melanoma cells with the MART-1 epitope. Thus, the very frequently used MART-1 epitope was not expressed on the surface of many melanoma cell lines. Our data emphasize that the selected tumor antigens and/or epitopes are critical for the outcome of anti-cancer immunotherapy.
- Find related publications in this database (using NLM MeSH Indexing)
- Antigens, Neoplasm - analysis Antigens, Neoplasm - immunology
- Antigens, Surface - analysis Antigens, Surface - immunology
- Cell Line, Tumor - chemistry Cell Line, Tumor - immunology
- Cytotoxicity Tests, Immunologic -
- Cytotoxicity, Immunologic -
- Epitopes - analysis Epitopes - immunology
- Epitopes, T-Lymphocyte - analysis Epitopes, T-Lymphocyte - immunology
- Granzymes - biosynthesis Granzymes - immunology
- HLA-A2 Antigen - immunology
- Humans -
- Immunodominant Epitopes - analysis Immunodominant Epitopes - immunology
- Interferon-gamma - secretion
- Melanoma - chemistry Melanoma - immunology
- NK Cell Lectin-Like Receptor Subfamily K - biosynthesis NK Cell Lectin-Like Receptor Subfamily K - immunology
- Neoplasm Proteins - analysis Neoplasm Proteins - immunology
- Pore Forming Cytotoxic Proteins - biosynthesis Pore Forming Cytotoxic Proteins - immunology
- Proto-Oncogene Proteins c-bcl-2 - immunology
- T-Lymphocytes, Cytotoxic - immunology
- Find related publications in this database (Keywords)
- Melan-A/MART-1
- Cytotox T-cells
- Melanoma
- Lysis
- Bcl-2