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[Cancer Research 65, 6435-6442, July 15, 2005]
© 2005 American Association for Cancer Research


Immunology

Human CTL Epitopes Prostatic Acid Phosphatase-3 and Six-Transmembrane Epithelial Antigen of Prostate-3 as Candidates for Prostate Cancer Immunotherapy

Arthur Machlenkin1, Adrian Paz2, Erez Bar Haim1, Ofir Goldberger1, Eran Finkel1, Boaz Tirosh1, Ilan Volovitz1, Ezra Vadai1, Gilles Lugassy3, Shmuel Cytron2, Francois Lemonnier4, Esther Tzehoval1 and Lea Eisenbach1

1 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel; Departments of 2 Urology and 3 Hematology, Barzilai Medical Center, Ashkelon, Israel; and 4 AIDS-Retrovirus Department, Antiviral Cellular Immunity Unit, Pasteur Institute, Paris, France

Requests for reprints: Lea Eisenbach, Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 972-8-9344-555; Fax: 972-8-934-4141; E-mail: lea.eisenbach{at}weizmann.ac.il.

Specific immunotherapy of prostate cancer may be an alternative or be complementary to other approaches for treatment of recurrent or metastasized disease. This study aims at identifying and characterizing prostate cancer–associated peptides capable of eliciting specific CTL responses in vivo. Evaluation of peptide-induced CTL activity in vitro was done following immunization of HLA-A2 transgenic (HHD) mice. An in vivo tumor rejection was tested by adoptive transfer of HHD immune lymphocytes to nude mice bearing human tumors. To confirm the existence of peptide-specific CTL precursors in human, lymphocytes from healthy and prostate cancer individuals were stimulated in vitro in the presence of these peptides and CTL activities were assayed. Two novel immunogenic peptides derived from overexpressed prostate antigens, prostatic acid phosphatase (PAP) and six-transmembrane epithelial antigen of prostate (STEAP), were identified; these peptides were designated PAP-3 and STEAP-3. Peptide-specific CTLs lysed HLA-A2.1+ LNCaP cells and inhibited tumor growth on adoptive immunotherapy. Furthermore, peptide-primed human lymphocytes derived from healthy and prostate cancer individuals lysed peptide-pulsed T2 cells and HLA-A2.1+ LNCaP cells. Based on the results presented herein, PAP-3 and STEAP-3 are naturally processed CTL epitopes possessing anti–prostate cancer reactivity in vivo and therefore may constitute vaccine candidates to be investigated in clinical trials.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Molecular Cancer Research Cancer Prevention Research
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Copyright © 2005 by the American Association for Cancer Research.