| Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity. | |
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MedLine Citation:
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PMID: 23025755 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Adoptive transfer of T cells genetically modified with tumour-specific T-cell receptors (TCR) is a promising novel approach in the treatment of cancer. We have previously isolated an allorestricted MHC class I-restricted TCR with specificity for Formin-like protein 1 (FMNL1) with potent activity against chronic lymphocytic leukaemia cells. CD4(+) T cells have been described to be highly important for tumour elimination although TCR derived from CD4(+) T cells with anti-tumour reactivity have been only rarely described. In this study we aimed to isolate MHC class-II-restricted CD4(+) T cells and TCR with specificity for leukaemia antigens. We used professional antigen-presenting cells pulsed with the leukaemia-associated and tumour-associated antigen FMNL1 for stimulation of autologous T cells in vitro. We isolated two CD4(+) HLA-DR-restricted T-cell clones and T-cell-derived TCR with so far unknown specificity but high reactivity against lymphoma cells and native malignant cells derived from HLA-matched patients with diverse leukaemias. Moreover, characterization of the TCR after TCR gene transfer revealed that specific characteristics of isolated TCR as reactivity in response to Toll-like receptors were transferable on effector cells. Our results have a major impact on the development of novel immunotherapies. They demonstrate that TCR with potent HLA-DR-restricted anti-leukaemic reactivity against so far undefined self-restricted antigens can be isolated from the healthy autorestricted CD4(+) T-cell repertoire and these TCR are highly interesting candidate tools for novel immunotherapies. |
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Authors:
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Luise U Weigand; Xiaoling Liang; Sabine Schmied; Sabine Mall; Richard Klar; Oliver J Stötzer; Christoph Salat; Katharina Götze; Josef Mautner; Christian Peschel; Angela M Krackhardt |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Immunology Volume: 137 ISSN: 1365-2567 ISO Abbreviation: Immunology Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-10-02 Completed Date: 2012-12-03 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0374672 Medline TA: Immunology Country: England |
Other Details:
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Languages: eng Pagination: 226-38 Citation Subset: IM |
Copyright Information:
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© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd. |
Affiliation:
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Medizinische Klinik III, Innere Medizin mit Schwerpunkt Hämatologie und Onkologie, Technische Universität München, Münich. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Lineage Cells, Cultured Histocompatibility Antigens Class II / immunology* Humans Leukemia, Lymphocytic, Chronic, B-Cell / immunology* Leukemia, Myeloid, Acute / immunology* Ligands Receptors, Antigen, T-Cell / immunology* T-Lymphocytes / cytology, immunology |
| Chemical | |
Reg. No./Substance:
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0/Histocompatibility Antigens Class II; 0/Ligands; 0/Receptors, Antigen, T-Cell |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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