PMID- 12473604
OWN - NLM
STAT- MEDLINE
DCOM- 20030121
LR  - 20180823
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 8
IP  - 12
DP  - 2002 Dec
TI  - Screening of HLA-A24-restricted epitope peptides from prostate-specific membrane 
      antigen that induce specific antitumor cytotoxic T lymphocytes.
PG  - 3885-92
AB  - PURPOSE: Prostate-specific membrane antigen (PSMA), which is a transmembrane 
      glycoprotein predominantly expressed in prostate cancer, is an attractive target 
      for tumor-specific immunotherapy. To identify human leukocyte antigen 
      (HLA)-A24-restricted epitope peptides from PSMA for further application of the 
      dendritic cell (DC)-based immunotherapy targeting prostate cancer, we have 
      screened several PSMA-encoded HLA-A24-binding peptides for their capabilities to 
      elicit specific antitumor CTL response in vitro. EXPERIMENTAL DESIGN: The amino 
      acid sequence of PSMA was screened for peptides consisting of 9 or 10 amino 
      acids, which possess the known HLA-A24-binding motif. Nine candidate peptides 
      were screened for binding to HLA-A24 molecules. Then, each of these nine peptides 
      was studied to determine whether CTL responses could be induced by primary in 
      vitro immunization of CD8(+) T cells using peptide-pulsed autologous DCs derived 
      from peripheral blood mononuclear cells of HLA-A24(+) healthy donor as 
      antigen-presenting cells. The antigen specificity of the CTL lines was confirmed 
      using several tumor cell lines as target cells, which were genetically modified 
      to express both HLA-A24 and PSMA. RESULTS: Two peptides, LYSDPADYF and NYARTEDFF, 
      were demonstrated to elicit CTL lines that lyse peptide-pulsed, HLA-A24(+) 
      B-lymphoblastoid cells. Each of the CTL lines recognized their specific 
      PSMA-expressing target cells in a HLA-A24-restricted manner. The capability to 
      release IFN-gamma by the CTL lines was specifically inhibited by anti-MHC class I 
      and anti-CD8 monoclonal antibodies but not by anti-MHC class II and anti-CD4 
      monoclonal antibodies. CONCLUSION: Two novel HLA-A24-restricted PSMA-derived 
      epitopes were identified in this study. These epitopes can be used to further 
      evaluate the clinical utility of DC-based immunotherapeutic strategies for 
      treatment of hormone-refractory prostate cancers.
FAU - Horiguchi, Yutaka
AU  - Horiguchi Y
AD  - Department of Urology, School of Medicine, Keio University, Tokyo 160-8582, 
      Japan.
FAU - Nukaya, Ikuei
AU  - Nukaya I
FAU - Okazawa, Kazuhide
AU  - Okazawa K
FAU - Kawashima, Ichiro
AU  - Kawashima I
FAU - Fikes, John
AU  - Fikes J
FAU - Sette, Allesandro
AU  - Sette A
FAU - Tachibana, Masaaki
AU  - Tachibana M
FAU - Takesako, Kazutoh
AU  - Takesako K
FAU - Murai, Masaru
AU  - Murai M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Antigens, Surface)
RN  - 0 (Epitopes)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Oligopeptides)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.- (Carboxypeptidases)
RN  - EC 3.4.17.21 (FOLH1 protein, human)
RN  - EC 3.4.17.21 (Glutamate Carboxypeptidase II)
SB  - IM
MH  - Antigen-Presenting Cells/immunology
MH  - Antigens, Neoplasm/*chemistry/*immunology
MH  - *Antigens, Surface
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Carboxypeptidases/*chemistry
MH  - Cytotoxicity, Immunologic
MH  - Epitopes/*pharmacology
MH  - Glutamate Carboxypeptidase II
MH  - HLA-A Antigens/*metabolism
MH  - HLA-A24 Antigen
MH  - Humans
MH  - Immunotherapy
MH  - Interferon-gamma/pharmacology
MH  - Lymphoma, B-Cell/immunology
MH  - Male
MH  - Oligopeptides/*pharmacology
MH  - Prostatic Neoplasms/*immunology/therapy
MH  - T-Lymphocytes, Cytotoxic/*immunology
MH  - Tumor Cells, Cultured/drug effects/immunology
EDAT- 2002/12/11 04:00
MHDA- 2003/01/22 04:00
CRDT- 2002/12/11 04:00
PHST- 2002/12/11 04:00 [pubmed]
PHST- 2003/01/22 04:00 [medline]
PHST- 2002/12/11 04:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2002 Dec;8(12):3885-92.