Human CTL epitopes prostatic acid phosphatase-3 and six-transmembrane epithelial antigen of prostate-3 as candidates for prostate cancer immunotherapy
Autor: | Ilan Volovitz, François Lemonnier, Shmuel Cytron, Erez Bar Haim, Lea Eisenbach, Eran Finkel, Ezra Vadai, Ofir Goldberger, Arthur Machlenkin, Gilles Lugassy, Esther Tzehoval, Boaz Tirosh, Adrian Paz |
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Rok vydání: | 2005 |
Předmět: |
Male
Cancer Research Adoptive cell transfer medicine.medical_treatment Acid Phosphatase Epitopes T-Lymphocyte Mice Nude chemical and pharmacologic phenomena Mice Transgenic Immunotherapy Adoptive Prostate cancer Mice Antigen Prostate Antigens Neoplasm Cell Line Tumor LNCaP HLA-A2 Antigen medicine Animals Humans Amino Acid Sequence Mice Knockout business.industry Prostatic Neoplasms Immunotherapy medicine.disease Xenograft Model Antitumor Assays Peptide Fragments CTL medicine.anatomical_structure Oncology Prostatic acid phosphatase Immunology Protein Tyrosine Phosphatases business Oxidoreductases T-Lymphocytes Cytotoxic |
Zdroj: | Cancer research. 65(14) |
ISSN: | 0008-5472 |
Popis: | 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. |
Databáze: | OpenAIRE |
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