Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells

Ohkuri, Takayuki; Wakita, Daiko; Chamoto, Kenji; Togashi, Yuji; Kitamura, Hiroyuki; Nishimura, Takashi

doi:10.1038/sj.bjc.6604966

Cited by 20 publications

(17 citation statements)

References 42 publications

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“…To date, phase I cancer immunotherapy clinical studies that targeted the WT1 protein have been conducted for AML, MDS, lung, and breast cancer (22,23,31) and phase I/II clinical studies using WT1 peptides have been conducted for patients with various types of cancer (29). It was reported that the increase in the numbers of WT1-specific CTLs in cancer patients after vaccination with WT1 peptides closely correlates with the therapeutic efficacy against cancer (7,16,17,20). Therefore, monitoring antitumor immune responses, particularly the generation of tumor-specific CTLs, is critical for accurate assessments of the efficacy of cancer vaccine immunotherapy.…”

Section: Methodsmentioning

confidence: 99%

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

et al. 2013

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Wilms' tumor gene 1 (WT1) has been proposed as an attractive target for cancer immunotherapy. A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes. This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02. This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs. Here we induced several WT1 CTLs that reacted with both modified and natural WT1 tetramers from peripheral blood mononuclear cells. Then, T-cell receptor (TCR) genes were isolated from these WT1 CTLs to determine their Vα and Vβ usage. These TCR genes were transduced into human T lymphoma cells to establish a stable cell line, SK37, which expressed a WT1-specific TCR. We confirmed that SK37 cells reacted with both modified and natural WT1 tetramers, which indicated that SK37 cells could be a useful tool for WT1 tetramer reagent quality assurance. One the basis of these findings, we propose that this WT1 tetramer, which was quality-assured using established SK37 cells, will contribute to reliable immunomonitoring of tumor-specific CTL responses of cancer patients who receive WT1-targeted cancer vaccine therapy or TCR-gene therapy.

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Section: Methodsmentioning

confidence: 99%

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

et al. 2013

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“…PBMCs were obtained from healthy individuals by Ficoll-Hypaque (Amersham Bioscience, Uppsala, Sweden) gradient centrifugation after obtaining their informed consent. PBMCs (2 3 10 5 cells) were cultured with AIM-V (Invitrogen, Carlsbad, CA) in the presence of recombinant human IL-4 or IL-3 plus GM-CSF for 7 d, as described previously (37). We evaluated phenotypes of the generated human DCs.…”

Section: Generation Of Human Dcs From Pbmcsmentioning

confidence: 99%

Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor

Kitamura

Kobayashi

Wakita

et al. 2012

The Journal of Immunology

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Neurokinin A (NKA), a neurotransmitter distributed in the central and peripheral nervous system, strictly controls vital responses, such as airway contraction, by intracellular signaling through neurokinin-2 receptor (NK2R). However, the function of NKA–NK2R signaling on involvement in immune responses is less-well defined. We demonstrate that NK2R-mediated neuropeptide signaling activates dendritic cell (DC)-mediated type 1 immune responses. IFN-γ stimulation significantly induced NK2R mRNA and remarkably enhanced surface protein expression levels of bone marrow-derived DCs. In addition, the DC-mediated NKA production level was significantly elevated after IFN-γ stimulation in vivo and in vitro. We found that NKA treatment induced type 1 IFN mRNA expressions in DCs. Transduction of NK2R into DCs augmented the expression level of surface MHC class II and promoted Ag-specific IL-2 production by CD4+ T cells after NKA stimulation. Furthermore, blockade of NK2R by an antagonist significantly suppressed IFN-γ production by both CD4+ T and CD8+ T cells stimulated with the Ag-loaded DCs. Finally, we confirmed that stimulation with IFN-γ or TLR3 ligand (polyinosinic-polycytidylic acid) significantly induced both NK2R mRNA and surface protein expression of human PBMC-derived DCs, as well as enhanced human TAC1 mRNA, which encodes NKA and Substance P. Thus, these findings indicate that NK2R-dependent neuropeptide signaling regulates Ag-specific T cell responses via activation of DC function, suggesting that the NKA–NK2R cascade would be a promising target in chronic inflammation caused by excessive type 1-dominant immunity.

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“…Early studies reported the identification of CTL epitopes [34][35][36] and T helper epitopes derived from MAGE-4 antigen [37]. HLA-A2 is the most common HLA-A supertype in most of the populations, particularly in Asian population with an estimated frequency of more than 40% [38].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel CD8+ T Cell Epitope Derived from Cancer‐Testis Antigen MAGE‐4 in Oesophageal Carcinoma

Gao

et al. 2011

Scand J Immunol

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MAGE‐4 is considered as an attractive cancer‐testis (CT) antigen for tumour immunotherapy, and it is overexpressed in oesophageal carcinoma (EC). To identify MAGE‐4‐derived HLA‐A2 restricted epitopes, native peptides and their analogues were predicted with prediction programs. The native peptide, p286 (KVLEHVVRV), and its analogues, p286‐1Y2L and p286‐1Y2L9L, showed potent binding affinity and stability towards HLA‐A*0201 molecule. Cytotoxic T lymphocytes (CTLs) induced by p286‐1Y2L9L could release IFN‐γ in ELISPOT assay. In cytotoxicity assay, p286‐1Y2L9L showed the capability to induce specific CTLs which could lyse the target cancer cells from both PBMCs of healthy donors and HLA‐A2.1/Kb transgenic mice. Our results indicated that the peptide p286‐1Y2L9L could serve as a novel candidate epitope to develop peptide vaccines against oesophageal carcinoma.

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Identification of novel helper epitopes of MAGE-A4 tumour antigen: useful tool for the propagation of Th1 cells

Cited by 20 publications

References 42 publications

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

Neuropeptide Signaling Activates Dendritic Cell-Mediated Type 1 Immune Responses through Neurokinin-2 Receptor

Identification of a Novel CD8+ T Cell Epitope Derived from Cancer‐Testis Antigen MAGE‐4 in Oesophageal Carcinoma

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