Identification of naturally processed helper T-cell epitopes from prostate-specific membrane antigen using peptide-based in vitro stimulation.
OBJECTIVE
There is growing evidence that CD4(+) helper T lymphocytes (HTLs) play an essential role in the induction and long-term maintenance of antitumor CTL responses. Thus, approaches to develop effective T-cell-based immunotherapy should focus in the stimulation of both CTLs and HTLs reactive against tumor-associated antigens. The present studies were performed with the purpose of identifying HTL epitopes for prostate-specific membrane antigen (PSMA) for the optimization of vaccines for prostate cancer.


METHODS
Synthetic peptides from regions of the PSMA sequence that were predicted to serve as HTL epitopes were prepared with use of computer-based algorithms and tested for their capacity to trigger in vitro HTL responses in lymphocytes from normal volunteers.


RESULTS
Our results show that 4 peptides from PSMA were effective in eliciting HTL responses. Moreover, HTL reactive to 3 of the 4 peptides were capable of reacting with naturally processed antigen in the form of freeze/thaw lysates or apoptotic cells produced from PSMA-positive LNCaP tumor cell lines.


CONCLUSIONS
Human HTLs are capable of effectively recognizing epitopes derived from PSMA. The information presented here should facilitate the design of improved vaccination strategies for prostate cancer.
Kobayashi
Hiroya
H
Department of Immunology, Mayo Clinic, Rochester, Minnesota55905, USA.
Omiya
Ryusuke
R
Sodey
Benjamin
B
Yanai
Mitsuru
M
Oikawa
Kensuke
K
Sato
Keisuke
K
Kimura
Shoji
S
Senju
Satoru
S
Nishimura
Yasuharu
Y
Tateno
Masatoshi
M
Celis
Esteban
E
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D043425:Glutamate Carboxypeptidase II / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*
D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II