title: A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.
abstract: Immunotherapies such as adoptive transfer of T cells or natural killer cells, or monoclonal antibody (MoAb) treatment have recently been recognized as effective means to treat cancer patients. However, adoptive transfer of B cells or plasma cells producing tumor-specific antibodies has not been applied as a therapy because long-term culture and selective expansion of antigen-specific B cells has been technically very difficult. Here, we describe a novel cancer immunotherapy that uses B-cell adoptive transfer. We demonstrate that germinal-center-like B cells (iGB cells) induced in vitro from mouse naïve B cells become plasma cells and produce IgG antibodies for more than a month in the bone marrow of non-irradiated recipient mice. When transferred into mice, iGB cells producing antibody against a surrogate tumor antigen suppressed lung metastasis and growth of mouse melanoma cells expressing the same antigen and prolonged survival of the recipients. In addition, we have developed a novel culture system called FAIS to selectively expand antigen-specific iGB cells utilizing the fact that iGB cells are sensitive to Fas-induced cell death unless their antigen receptors are ligated by membrane-bound antigens. The selected iGB cells efficiently suppressed lung metastasis of melanoma cells in the adoptive immunotherapy model. As human blood B cells can be propagated as iGB cells using culture conditions similar to the mouse iGB cell cultures, our data suggest that it will be possible to treat cancer-bearing patients by the adoptive transfer of cancer-antigen-specific iGB cells selected in vitro. This new adoptive immunotherapy should be an alternative to the laborious development of MoAb drugs against cancers for which no effective treatments currently exist.
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Moutai
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamana
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Nojima
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences (RIBS), Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008545:Melanoma / Q000628:therapy; D051379:Mice; D008817:Mice, Mutant Strains