Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein trp-p8.
BACKGROUND
New concepts for the immunotherapy of prostate carcinoma (PCa) largely depend on the identification of suitable target antigens that are present in a high percentage of prostate tumors. Their expression in normal tissues should be restricted to the prostate and they should be immunogenic in vivo. The number of antigens displaying these properties is still limited. Here, we identify for the first time an immunogenic peptide derived from the prostate-specific protein transient receptor potential-p8 (trp-p8) that is recognized by cytotoxic T lymphocytes (CTLs) from PCa patients.


METHODS
To determine the abundance of trp-p8 in prostate tumors, the expression level of trp-p8 mRNA was quantitatively analyzed in a panel of prostate cancer tissues. Trp-p8-derived human leukocyte antigen (HLA)-A*0201-restricted peptides were selected and tested for the in vitro activation of CTLs when loaded on autologous dendritic cells (DCs).


RESULTS
Trp-p8 mRNA was found to be expressed in all prostate tumors and in the corresponding normal prostate tissue. Of five selected trp-p8-derived peptides, only peptide GLMKYIGEV was shown to activate specific CTLs, which effectively lysed PCa cells confirming the endogenous generation and presentation of this peptide by tumor cells.


CONCLUSIONS
Our results suggest this antigen as a suitable target for the T-cell-based immunotherapy of PCa.
Kiessling
Andrea
A
Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany.
Füssel
Susanne
S
Schmitz
Marc
M
Stevanovic
Stefan
S
Meye
Axel
A
Weigle
Bernd
B
Klenk
Ulrich
U
Wirth
Manfred P
MP
Rieber
Ernst P
EP
D000951:Antigens, Neoplasm / Q000276:immunology*; D003713:Dendritic Cells; D015972:Gene Expression Regulation, Neoplastic; D015234:HLA-A Antigens / Q000276:immunology*; D015789:HLA-A2 Antigen; D006801:Humans; D007167:Immunotherapy; D007473:Ion Channels / Q000096:biosynthesis* / Q000276:immunology*; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000276:immunology*; D010455:Peptides; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D050053:TRPM Cation Channels
D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D007473:Ion Channels; D009363:Neoplasm Proteins; D010455:Peptides; D012333:RNA, Messenger; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human