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Experimental Therapeutics, Preclinical Pharmacology |
Department of Immunology, Mayo Clinic, Rochester, Minnesota [H. K., R. O., B. S., E. C.]; Department of Pathology, Asahikawa Medical College, Asahikawa, Japan [H. K., M. Y., K. O., K. S., S. K., M. T.]; and Division of Immunogenetics, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Science, Kumamoto, Japan [S. S., Y. N.]
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.
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