Identification of Naturally Processed Helper T-Cell Epitopes from Prostate-Specific Membrane Antigen Using Peptide-Based in Vitro Stimulation

Hiroya Kobayashi, Ryusuke Omiya, Benjamin Sodey, Mitsuru Yanai, Kensuke Oikawa, Keisuke Sato, Shoji Kimura, Satoru Senju, Yasuharu Nishimura, Masatoshi Tateno, Esteban Celis

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)5386-5393
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number14
StatePublished - Nov 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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