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Open Access Green as soon as Postprint is submitted to ZB.
Isolation of human MHC class II-restricted T cell receptors from the autologous T-cell repertoire with potent anti-leukaemic reactivity.
Immunology 137, 226-238 (2012)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
leukaemia; lymphoma; myeloma; MHC; HLA; T-cell receptor (TCR); therapy; immunotherapy; toll receptors; Toll-like receptors; ENHANCED ANTITUMOR-ACTIVITY; HUMAN-LYMPHOCYTES; TUMOR-ANTIGEN; PEPTIDE; TCR; MELANOMA; IMMUNITY; TRANSPLANTATION; AUTOIMMUNITY; VACCINATION
ISSN (print) / ISBN
0019-2805
e-ISSN
1365-2567
Journal
Immunology
Quellenangaben
Volume: 137,
Issue: 3,
Pages: 226-238
Publisher
Wiley
Non-patent literature
Publications
Reviewing status
Peer reviewed