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.
Highlights
Immunotherapy has recently become more widely accepted as an effective means to treat cancer patients
We showed previously that the induced GC B (iGB) cells differentiate to plasma cells in the bone marrow (BM) when they were transferred into irradiated mice
Based on results using our mouse model, here we propose a new system of adoptive transfer cancer immunotherapy using B cells
Summary
Immunotherapy has recently become more widely accepted as an effective means to treat cancer patients. The main player in cell-mediated cancer immunotherapy has been cytotoxic T lymphocytes (CTLs) directed against tumor cells, which recognize via their T-cell receptor (TCR) a particular peptide derived from a tumor antigen (Ag) presented by MHC I on the tumor cells. Such T cells from excised tumor tissues or patients’ blood are selectively expanded in vitro on syngeneic Ag presenting cells (APCs) expressing the tumor Ag with cytokines like IL-2 and transferred back into the patients [1,2]. These therapies based on adoptive cell transfer have far not been commonly adopted as an option for cancer therapy since their clinical success has been limited while they require time-consuming laboratory work, including individual cell culture for several weeks in a quality-controlled clean room
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