TY - JOUR

T1 - The immunodominant HLA-A2-restricted MART-1 epitope is not presented on the surface of many melanoma cell lines

AU - Sørensen, Rikke Baek

AU - Junker, Niels

AU - Kirkin, Alexei

AU - Voigt, Heike

AU - Svane, Inge Marie

AU - Becker, Jürgen C

AU - thor Straten, Per

AU - Andersen, Mads Hald

N1 - Keywords: Antigens, Neoplasm; Antigens, Surface; Cell Line, Tumor; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Epitopes; Epitopes, T-Lymphocyte; Granzymes; HLA-A2 Antigen; Humans; Immunodominant Epitopes; Interferon-gamma; Melanoma; NK Cell Lectin-Like Receptor Subfamily K; Neoplasm Proteins; Pore Forming Cytotoxic Proteins; Proto-Oncogene Proteins c-bcl-2; T-Lymphocytes, Cytotoxic

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1007/s00262-008-0588-0

DO - 10.1007/s00262-008-0588-0

M3 - Journal article

C2 - 18828018

VL - 58

SP - 665

EP - 675

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

SN - 0340-7004

IS - 5

ER -