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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
Author(s) -
Yao Akihisa,
Harada Mamoru,
Matsueda Satoko,
Ishihara Yuki,
Shomura Hiroki,
Takao Yukari,
Noguchi Masanori,
Matsuoka Kei,
Hara Isao,
Kamidono Sadao,
Itoh Kyogo
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20133
Subject(s) - prostate cancer , parathyroid hormone related protein , cytotoxic t cell , medicine , prostate , cancer , lncap , cancer research , immunotherapy , peripheral blood mononuclear cell , peptide , malignancy , immunology , parathyroid hormone , biology , biochemistry , in vitro , calcium
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 PTHrP 59–67 and PTHrP 42–51 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 PTHrP 42–51 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. © 2004 Wiley‐Liss, Inc.