Substitution analog peptide derived from HER-2 can efficiently induce HER-2-specific, HLA-A24 restricted CTLs.
Identifieur interne : 002089 ( PubMed/Checkpoint ); précédent : 002088; suivant : 002090Substitution analog peptide derived from HER-2 can efficiently induce HER-2-specific, HLA-A24 restricted CTLs.
Auteurs : Kousaku Mimura [Japon] ; Koji Kono ; Scott Southwood ; John Fikes ; Akihiro Takahashi ; Naoto Miyagawa ; Hidemitsu Sugai ; Hideki FujiiSource :
- Cancer immunology, immunotherapy : CII [ 0340-7004 ] ; 2006.
Descripteurs français
- KwdFr :
- Agranulocytes (cytologie), Allèles, Antigène HLA-A24, Antigènes HLA-A (), Antigènes néoplasiques (métabolisme), Cellules dendritiques (cytologie), Concentration inhibitrice 50, Cytotoxicité immunologique, Déterminants antigéniques des lymphocytes T (), Humains, Lignée cellulaire tumorale, Lymphocytes T cytotoxiques (), Peptides (), Récepteur ErbB-2 ().
- MESH :
- cytologie : Agranulocytes, Cellules dendritiques.
- métabolisme : Antigènes néoplasiques.
- Allèles, Antigène HLA-A24, Antigènes HLA-A, Concentration inhibitrice 50, Cytotoxicité immunologique, Déterminants antigéniques des lymphocytes T, Humains, Lignée cellulaire tumorale, Lymphocytes T cytotoxiques, Peptides, Récepteur ErbB-2.
English descriptors
- KwdEn :
- Alleles, Antigens, Neoplasm (metabolism), Cell Line, Tumor, Cytotoxicity, Immunologic, Dendritic Cells (cytology), Epitopes, T-Lymphocyte (chemistry), HLA-A Antigens (chemistry), HLA-A24 Antigen, Humans, Inhibitory Concentration 50, Leukocytes, Mononuclear (cytology), Peptides (chemistry), Receptor, ErbB-2 (chemistry), T-Lymphocytes, Cytotoxic (chemistry).
- MESH :
- chemical , chemistry : Epitopes, T-Lymphocyte, HLA-A Antigens, Peptides, Receptor, ErbB-2.
- chemical , metabolism : Antigens, Neoplasm.
- chemistry : T-Lymphocytes, Cytotoxic.
- cytology : Dendritic Cells, Leukocytes, Mononuclear.
- Alleles, Cell Line, Tumor, Cytotoxicity, Immunologic, HLA-A24 Antigen, Humans, Inhibitory Concentration 50.
Abstract
In order to broaden the possibility for anti-HER-2/neu (HER-2) immune targeting, it is important to identify HLA-A24 restricted peptide epitopes derived from HER-2, since HLA-A24 is one of the most common alleles in Japanese and Asian people. In the present study, we have screened HER-2-derived, HLA-A24 binding peptides for cytotoxic T lymphocyte (CTL) epitopes. A panel of HER-2-derived peptides with HLA-A24 binding motifs and the corresponding analogs designed to enhance HLA-A24 binding affinity were selected. Identification of HER-2-reactive and HLA-A24 restricted CTL epitopes were performed by a reverse immunology approach. To induce HER-2-reactive and HLA-A24 restricted CTLs, PBMCs from healthy donors were repeatedly stimulated with monocytes-derived, mature DCs pulsed with HER-2 peptide. Subsequent peptide-induced T cells were tested for the specificity by enzyme linked immunospot, cytotoxicity and tetramer assays. CTL clones were then obtained from the CTL lines by limiting dilution. Of the peptides containing HLA-A24 binding motifs, 16 peptides (nine mers) including wild type peptides (IC50 <1,000 nM) and substituted analog peptides (IC50 <50 nM) were selected for the present study. Our studies show that an analog peptide, HER-2(905AA), derived from HER-2(905) could efficiently induce HER-2-reactive and HLA-A24 restricted CTLs. The reactivity of the HER-2(905AA)-induced CTL (CTL905AA) was confirmed by different CTL assays. The CTL905AA clones also were able to lyse HER-2(+), HLA-A24(+) tumor cells and cytotoxicity could be significantly reduced in cold target inhibition assays using cold targets pulsed with the HER-2(905) wild type peptide as well as the inducing HER-2(905AA) analog peptide. A newly identified HER-2(905) peptide epitope is naturally processed and presented as a CTL epitope on HER-2 overexpressing tumor cells, and an MHC anchor-substituted analog, HER-2(905AA), can efficiently induce HER-2-specific, HLA-A24 restricted CTLs.
DOI: 10.1007/s00262-006-0123-0
PubMed: 16435129
Affiliations:
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pubmed:16435129Le document en format XML
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<term>Dendritic Cells (cytology)</term>
<term>Epitopes, T-Lymphocyte (chemistry)</term>
<term>HLA-A Antigens (chemistry)</term>
<term>HLA-A24 Antigen</term>
<term>Humans</term>
<term>Inhibitory Concentration 50</term>
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<term>Antigènes néoplasiques (métabolisme)</term>
<term>Cellules dendritiques (cytologie)</term>
<term>Concentration inhibitrice 50</term>
<term>Cytotoxicité immunologique</term>
<term>Déterminants antigéniques des lymphocytes T ()</term>
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<term>Lignée cellulaire tumorale</term>
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<term>Peptides ()</term>
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<term>Cellules dendritiques</term>
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<front><div type="abstract" xml:lang="en">In order to broaden the possibility for anti-HER-2/neu (HER-2) immune targeting, it is important to identify HLA-A24 restricted peptide epitopes derived from HER-2, since HLA-A24 is one of the most common alleles in Japanese and Asian people. In the present study, we have screened HER-2-derived, HLA-A24 binding peptides for cytotoxic T lymphocyte (CTL) epitopes. A panel of HER-2-derived peptides with HLA-A24 binding motifs and the corresponding analogs designed to enhance HLA-A24 binding affinity were selected. Identification of HER-2-reactive and HLA-A24 restricted CTL epitopes were performed by a reverse immunology approach. To induce HER-2-reactive and HLA-A24 restricted CTLs, PBMCs from healthy donors were repeatedly stimulated with monocytes-derived, mature DCs pulsed with HER-2 peptide. Subsequent peptide-induced T cells were tested for the specificity by enzyme linked immunospot, cytotoxicity and tetramer assays. CTL clones were then obtained from the CTL lines by limiting dilution. Of the peptides containing HLA-A24 binding motifs, 16 peptides (nine mers) including wild type peptides (IC50 <1,000 nM) and substituted analog peptides (IC50 <50 nM) were selected for the present study. Our studies show that an analog peptide, HER-2(905AA), derived from HER-2(905) could efficiently induce HER-2-reactive and HLA-A24 restricted CTLs. The reactivity of the HER-2(905AA)-induced CTL (CTL905AA) was confirmed by different CTL assays. The CTL905AA clones also were able to lyse HER-2(+), HLA-A24(+) tumor cells and cytotoxicity could be significantly reduced in cold target inhibition assays using cold targets pulsed with the HER-2(905) wild type peptide as well as the inducing HER-2(905AA) analog peptide. A newly identified HER-2(905) peptide epitope is naturally processed and presented as a CTL epitope on HER-2 overexpressing tumor cells, and an MHC anchor-substituted analog, HER-2(905AA), can efficiently induce HER-2-specific, HLA-A24 restricted CTLs.</div>
</front>
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<Abstract><AbstractText>In order to broaden the possibility for anti-HER-2/neu (HER-2) immune targeting, it is important to identify HLA-A24 restricted peptide epitopes derived from HER-2, since HLA-A24 is one of the most common alleles in Japanese and Asian people. In the present study, we have screened HER-2-derived, HLA-A24 binding peptides for cytotoxic T lymphocyte (CTL) epitopes. A panel of HER-2-derived peptides with HLA-A24 binding motifs and the corresponding analogs designed to enhance HLA-A24 binding affinity were selected. Identification of HER-2-reactive and HLA-A24 restricted CTL epitopes were performed by a reverse immunology approach. To induce HER-2-reactive and HLA-A24 restricted CTLs, PBMCs from healthy donors were repeatedly stimulated with monocytes-derived, mature DCs pulsed with HER-2 peptide. Subsequent peptide-induced T cells were tested for the specificity by enzyme linked immunospot, cytotoxicity and tetramer assays. CTL clones were then obtained from the CTL lines by limiting dilution. Of the peptides containing HLA-A24 binding motifs, 16 peptides (nine mers) including wild type peptides (IC50 <1,000 nM) and substituted analog peptides (IC50 <50 nM) were selected for the present study. Our studies show that an analog peptide, HER-2(905AA), derived from HER-2(905) could efficiently induce HER-2-reactive and HLA-A24 restricted CTLs. The reactivity of the HER-2(905AA)-induced CTL (CTL905AA) was confirmed by different CTL assays. The CTL905AA clones also were able to lyse HER-2(+), HLA-A24(+) tumor cells and cytotoxicity could be significantly reduced in cold target inhibition assays using cold targets pulsed with the HER-2(905) wild type peptide as well as the inducing HER-2(905AA) analog peptide. A newly identified HER-2(905) peptide epitope is naturally processed and presented as a CTL epitope on HER-2 overexpressing tumor cells, and an MHC anchor-substituted analog, HER-2(905AA), can efficiently induce HER-2-specific, HLA-A24 restricted CTLs.</AbstractText>
</Abstract>
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<ForeName>Kousaku</ForeName>
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<name sortKey="Kono, Koji" sort="Kono, Koji" uniqKey="Kono K" first="Koji" last="Kono">Koji Kono</name>
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<name sortKey="Southwood, Scott" sort="Southwood, Scott" uniqKey="Southwood S" first="Scott" last="Southwood">Scott Southwood</name>
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