A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.
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 appl...
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doaj-91309255c4c0445aa707c2faf4c05c9b2020-11-24T21:51:08ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9273210.1371/journal.pone.0092732A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro.Tatsuya MoutaiHideyuki YamanaTakuya NojimaDaisuke KitamuraImmunotherapies 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.http://europepmc.org/articles/PMC3960256?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tatsuya Moutai Hideyuki Yamana Takuya Nojima Daisuke Kitamura |
spellingShingle |
Tatsuya Moutai Hideyuki Yamana Takuya Nojima Daisuke Kitamura A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro. PLoS ONE |
author_facet |
Tatsuya Moutai Hideyuki Yamana Takuya Nojima Daisuke Kitamura |
author_sort |
Tatsuya Moutai |
title |
A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro. |
title_short |
A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro. |
title_full |
A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro. |
title_fullStr |
A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro. |
title_full_unstemmed |
A novel and effective cancer immunotherapy mouse model using antigen-specific B cells selected in vitro. |
title_sort |
novel and effective cancer immunotherapy mouse model using antigen-specific b cells selected in vitro. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3960256?pdf=render |
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