Document Detail


Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity.
MedLine Citation:
PMID:  23025755     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Immunology     Volume:  137     ISSN:  1365-2567     ISO Abbreviation:  Immunology     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-03     Revised Date:  2013-11-05    
Medline Journal Info:
Nlm Unique ID:  0374672     Medline TA:  Immunology     Country:  England    
Other Details:
Languages:  eng     Pagination:  226-38     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.
Affiliation:
Medizinische Klinik III, Innere Medizin mit Schwerpunkt Hämatologie und Onkologie, Technische Universität München, Münich.
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MeSH Terms
Descriptor/Qualifier:
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:
0/Histocompatibility Antigens Class II; 0/Ligands; 0/Receptors, Antigen, T-Cell
Comments/Corrections

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