Transduction of a novel HLA-DRB1*04:05-restricted, WT1-specific TCR gene into human CD4+ T cells confers killing activity against human leukemia cells.
OBJECTIVE
Wilms' tumor gene 1 (WT1) product is a pan-tumor-associated antigen. We previously identified WT1 protein-derived promiscuous helper peptide, WT1332. Therefore, isolation and characterization of the WT1332-specific T-cell receptors (TCRs) are useful to develop broadly applicable TCR gene-based adoptive immunotherapy.


METHODS
A novel HLA-DRB1*04:05-restricted WT1332-specific TCR gene was cloned and transduced into human CD4+ T-cells by using a lentiviral vector.


RESULTS
The WT1332-specific TCR-transduced CD4+ T-cells showed strong proliferation and Th1-cytokine production in an HLA-DRB1*04:05-restricted, WT1332-specific manner. Furthermore, the WT1332-specific TCR-transduced CD4+ T-cells could lyse HLA-DRB1*04:05-positive, WT1-expressing leukemia cells in vitro.


CONCLUSIONS
The novel TCR gene cloned here should be a promising tool to develop adoptive immunotherapy of WT1332-specific TCR-transduced CD4+ T-cells for the treatment of WT1-expressing cancer, such as leukemia.
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Akiko
A
Katsuhara
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
Fumihiro
F
Fujiki
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Nao
N
Aoyama
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Satoe
S
Tanii
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
Soyoko
S
Morimoto
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Yoshihiro
Y
Oka
Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
Akihiro
A
Tsuboi
Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.
Hiroko
H
Nakajima
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Kenta
K
Kondo
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Naoya
N
Tatsumi
Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan.
Jun
J
Nakata
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
Yoshiki
Y
Nakae
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
Satoshi
S
Takashima
Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan.
Sumiyuki
S
Nishida
Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
Naoki
N
Hosen
Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd, Tokushima, Japan.
Shinji
S
Sogo
Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan.
Yusuke
Y
Oji
Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan sugiyama@sahs.med.osaka-u.ac.jp.
Haruo
H
Sugiyama
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D016207:Cytokines / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D019672:Genes, T-Cell Receptor; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive; D019169:Jurkat Cells; D007938:Leukemia / Q000628:therapy*; D008969:Molecular Sequence Data; D014161:Transduction, Genetic; D025721:WT1 Proteins / Q000276:immunology*
D016207:Cytokines; D059811:HLA-DRB1 Chains; C493960:HLA-DRB1*04:05 antigen; D025721:WT1 Proteins
HLA class II; HLA-DRB1*04:05; TCR gene therapy; Wilms' tumor gene (WT1); helper peptide