Induction of tumor specific cytotoxic T lymphocytes in prostate cancer using prostatic acid phosphatase derived HLA-A2402 binding peptide.
OBJECTIVE
Human prostatic acid phosphatase is a prostate specific differentiation antigen. Prostatic acid phosphatase levels increase in the serum of patients with prostate cancer and its peptide from positions 299 to 307 (PAP 299-307) is recognized by HLA-A2 restricted cytotoxic T lymphocytes. We investigated whether HLA-A2402 binding prostatic acid phosphatase derived peptides induce HLA-A2402 restricted, tumor specific cytotoxic T lymphocytes from the peripheral blood mononuclear cells of patients with prostate cancer.


METHODS
Peptide binding activity was measured with RMA-S-A*A2402 cell lines and flow cytometry. Cytotoxic T-lymphocyte activity of the peripheral blood mononuclear cells of patients with prostate cancer and healthy donors was measured by interferon-gamma and (51)creatinine release assays. Prostatic acid phosphatase expression in the tumor cell lines at the messenger RNA and protein levels was investigated by reverse transcriptase-polymerase chain reaction and immunohistochemical analysis, respectively.


RESULTS
An HLA-A2402 binding, prostatic acid phosphatase derived peptide consisting of the prostatic acid phosphatase amino acid sequence from positions 213 to 221 (PAP 213-221, LYCESVHNF) showed the ability to induce HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes, which are cytoxic to prostatic acid phosphatase positive tumor cells from the peripheral blood mononuclear cells of patients with prostate cancer.


CONCLUSIONS
PAP 213-221 may be appropriate as a cancer vaccine for specific immunotherapy in patients with HLA-A2402 positive prostate cancer.
Inoue
Y
Y
Pharmacology Division, Department of Urology, Transplantation Unit, National Cancer Center, Chuo-ku, Tokyo, Japan.
Takaue
Y
Y
Takei
M
M
Kato
K
K
Kanai
S
S
Harada
Y
Y
Tobisu
K
K
Noguchi
M
M
Kakizoe
T
T
Itoh
K
K
Wakasugi
H
H
D000135:Acid Phosphatase; D015234:HLA-A Antigens / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D008297:Male; D010455:Peptides; D011471:Prostatic Neoplasms / Q000276:immunology*; D017027:Protein Tyrosine Phosphatases / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015234:HLA-A Antigens; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010455:Peptides; D000135:Acid Phosphatase; C428439:prostatic acid phosphatase; D017027:Protein Tyrosine Phosphatases