Recognition of prostate and melanoma tumor cells by six-transmembrane epithelial antigen of prostate-specific helper T lymphocytes in a human leukocyte antigen class II-restricted manner.
The six-transmembrane epithelial antigen of prostate (STEAP) protein is an attractive candidate for T cell-based immunotherapy because it is overexpressed in prostate cancer and various other tumor types. Several peptide epitopes capable of stimulating CTLs that killed STEAP-expressing tumor cells have been described. Our goal was the identification of helper T lymphocyte (HTL) epitopes of STEAP for the optimization of T cell-based immunotherapies against STEAP-expressing malignancies. Candidate HTL epitopes for STEAP were predicted using in silico algorithms for HLA class II-binding peptides and were tested for their ability to elicit HTL responses by in vitro peptide vaccination of CD4 T lymphocytes from healthy individuals and prostate cancer patients. Two peptides (STEAP(102-116) and STEAP(192-206)) were effective in stimulating in vitro antitumor HTL responses in both normal individuals and prostate cancer patients. Notably, both STEAP HTL peptides behaved as promiscuous T-cell epitopes because they stimulated T cells in the context of more than one MHC class II allele. These newly described STEAP HTL epitopes could be of value for the design and optimization of T cell-based immunotherapy against STEAP-expressing tumors.
Kobayashi
Hiroya
H
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan.
Nagato
Toshihiro
T
Sato
Keisuke
K
Aoki
Naoko
N
Kimura
Shoji
S
Murakami
Masamoto
M
Iizuka
Hajime
H
Azumi
Makoto
M
Kakizaki
Hidehiro
H
Tateno
Masatoshi
M
Celis
Esteban
E
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology*; D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000951:Antigens, Neoplasm; D000939:Epitopes; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D010088:Oxidoreductases; C432763:STEAP1 protein, human