New epitope peptides derived from parathyroid hormone-related protein which have the capacity to induce prostate cancer-reactive cytotoxic T lymphocytes in HLA-A2+ prostate cancer patients.
BACKGROUND
Parathyroid hormone-related protein (PTHrP) is produced by cancer cells and has been suggested to be responsible for malignancy-associated hypercalcemia and osteolysis after bone metatsases. Therefore, PTHrP is a promising target in the treatment of metastatic prostate cancer.


METHODS
Seven PTHrP-derived peptides were prepared based on the HLA-A2 binding motif. These peptide candidates were screened by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs), and their ability to be recognized by immunoglobulin G (IgG).


RESULTS
Both the PTHrP59-67 and PTHrP42-51 peptides were found to efficiently induce peptide-specific CTLs from peripheral blood mononuclear cells of HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. These CTLs showed HLA-A2-restricted cytotoxicity toward prostate cancer cells. IgG reactive to the PTHrP42-51 peptide was frequently detected in prostate cancer patients.


CONCLUSIONS
These results indicate that these two new PTHrP peptides will be useful in the peptide-based immunotherapy of HLA-A2+ prostate cancer patients, especially those with bone metastases.
Yao
Akihisa
A
Department of Immunology, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Harada
Mamoru
M
Matsueda
Satoko
S
Ishihara
Yuki
Y
Shomura
Hiroki
H
Takao
Yukari
Y
Noguchi
Masanori
M
Matsuoka
Kei
K
Hara
Isao
I
Kamidono
Sadao
S
Itoh
Kyogo
K
D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D044162:Parathyroid Hormone-Related Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments