Establishment of a novel NFAT-GFP reporter platform useful for the functional avidity maturation of HLA class II-restricted TCRs.

Autor: Fujiki F; Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. fu-fuji@sahs.med.osaka-u.ac.jp.; Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan. fu-fuji@sahs.med.osaka-u.ac.jp., Morimoto S; Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Japan., Nishida Y; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Japan., Tanii S; Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Japan., Aoyama N; Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Japan., Inatome M; Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Japan., Inoue K; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Japan., Katsuhara A; Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Suita, Japan., Nakajima H; Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Nakata J; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Japan., Nishida S; Strategic Global Partnership & X (Cross)-Innovation Initiative, Graduate School of Medicine, Osaka University & Osaka University Hospital, Suita, Japan.; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan., Tsuboi A; Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan., Oka Y; Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Suita, Japan.; Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Japan., Oji Y; Department of Clinical Laboratory and Biomedical Sciences, Osaka University Graduate School of Medicine, Suita, Japan., Sogo S; Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.; Department of Research Management, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.; Joint Research Chair of Immune Therapeutic Drug Discovery IFReC, Osaka University Graduate School of Medicine, Suita, Japan., Sugiyama H; Department of Cancer Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2023 Jul; Vol. 72 (7), pp. 2347-2356. Date of Electronic Publication: 2023 Mar 20.
DOI: 10.1007/s00262-023-03420-8
Abstrakt: CD4 + T cells that recognize antigenic peptides presented on HLA class II are essential for inducing an optimal anti-tumor immune response, and adoptive transfer of tumor antigen-specific TCR-transduced CD4 + T cells with high responsiveness against tumor is a promising strategy for cancer treatment. Whereas a precise evaluation method of functional avidity, an indicator of T cell responsiveness against tumors, has been established for HLA class I-restricted TCRs, it remains unestablished for HLA class II-restricted TCRs. In this study, we generated a novel platform cell line, CD4-2D3, in which GFP reporter was expressed by NFAT activation via TCR signaling, for correctly evaluating functional avidity of HLA class II-restricted TCRs. Furthermore, using this platform cell line, we succeeded in maturating functional avidity of an HLA class II-restricted TCR specific for a WT1-derived helper peptide by substituting amino acids in complementarity determining region 3 (CDR3) of the TCR. Importantly, we demonstrated that transduction of an avidity-maturated TCR conferred strong cytotoxicity against WT1-expressing leukemia cells on CD4 + T cells, compared to that of its original TCR. Thus, CD4-2D3 cell line should be useful not only to evaluate TCR functional avidity in HLA class II-restricted TCRs but also to screen appropriate TCRs for clinical applications such as cancer immunotherapy.
(© 2023. The Author(s).)
Databáze: MEDLINE
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