title: Generation of anti-tumour effector T cells from naïve T cells by stimulation with dendritic/tumour fusion cells.
abstract: Tumour-draining lymph node T cells are an excellent source of effector T cells that can be used in adoptive tumour immunotherapy because they have already been sensitized to tumour-associated antigens in vivo. However, such tumour-specific immune cells are not readily obtained from the host due to poor immunogenicity of tumours and reduced host immune responses. One obstacle in implementation of adoptive immunotherapy has been insufficient sensitization and expansion of tumour-specific effector cells. In this study, we aim to improve adoptive immunotherapy by generating anti-tumour effector T cells from naïve T lymphocytes. We attempted to achieve this by harnessing the advantages of dendritic cell (DC)-based anti-cancer vaccine strategies. Electrofusion was routinely employed to produce fusion cells with 30-40% efficiency by using the poorly immunogenic murine B16/F10 cell line, D5 cells, and DC generated from bone marrow cells. CD62L-positive T cells from spleens of naïve mice and the fusion cells were cocultured with a low concentration of IL-2. After 9 days of culture, the antigen-specific T cells were identified with an upregulation of CD25 and CD69 expression and a downregulation of CD62L expression. These cells secreted IFN-gamma upon stimulation with irradiated tumour cells. Moreover, when transferred into mice with 3-day established pulmonary metastases, these cells with coadministration of IL-2 exhibited anti-tumour efficacy. In contrast, naïve T cells cocultured with a mixture of unfused DC and irradiated tumour cells did not exhibit anti-tumour efficacy. Our strategy provides the basis for a new approach in adoptive T cell immunotherapy for cancer.
authors.affiliation: Division of Respiratory Medicine, Department of Homeostatic Regulation and Development, Course for Biological Functions and Medical Control, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: T
authors.initials: T
authors.lastname: Hiura
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Matsuyama
authors.forename: H
authors.initials: H
authors.lastname: Kuriyama
authors.forename: J
authors.initials: J
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Kagamu
authors.forename: F
authors.initials: F
authors.lastname: Gejyo
authors.forename: H
authors.initials: H
authors.lastname: Yoshizawa
mesh_terms: D000818:Animals; D002459:Cell Fusion; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006822:Hybrid Cells / Q000276:immunology / Q000637:transplantation*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007371:Interferon-gamma