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Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model
Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti‐human podoplanin mAb, NZ‐1, and a rat–human chimeric anti‐human podoplanin antibody, NZ‐8, derived from NZ‐1, which induced antibody‐dependent cell...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021042/ https://www.ncbi.nlm.nih.gov/pubmed/27294401 http://dx.doi.org/10.1111/cas.12985 |
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author | Abe, Shinji Kaneko, Mika Kato Tsuchihashi, Yuki Izumi, Toshihiro Ogasawara, Satoshi Okada, Naoto Sato, Chiemi Tobiume, Makoto Otsuka, Kenji Miyamoto, Licht Tsuchiya, Koichiro Kawazoe, Kazuyoshi Kato, Yukinari Nishioka, Yasuhiko |
author_facet | Abe, Shinji Kaneko, Mika Kato Tsuchihashi, Yuki Izumi, Toshihiro Ogasawara, Satoshi Okada, Naoto Sato, Chiemi Tobiume, Makoto Otsuka, Kenji Miyamoto, Licht Tsuchiya, Koichiro Kawazoe, Kazuyoshi Kato, Yukinari Nishioka, Yasuhiko |
author_sort | Abe, Shinji |
collection | PubMed |
description | Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti‐human podoplanin mAb, NZ‐1, and a rat–human chimeric anti‐human podoplanin antibody, NZ‐8, derived from NZ‐1, which induced antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity against podoplanin‐positive MPM cell lines. In this study, we showed the antitumor effect of NZ‐1, NZ‐8, and NZ‐12, a novel rat–human chimeric anti‐human podoplanin antibody derived from NZ‐1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ‐1 and rat NK (CD161a(+)) cells inhibited the growth of tumors and the production of pleural effusion in NCI‐H290/PDPN or NCI‐H226 orthotopic xenograft mouse models. NZ‐8 and human natural killer (NK) (CD56(+)) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ‐12 induced potent ADCC mediated by human MNC, compared with either NZ‐1 or NZ‐8. Antitumor effects were observed following treatment with NZ‐12 and human NK (CD56(+)) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ‐12 mediated by human NK (CD56(+)) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin‐targeting immunotherapy using both NZ‐12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. |
format | Online Article Text |
id | pubmed-5021042 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50210422016-09-20 Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model Abe, Shinji Kaneko, Mika Kato Tsuchihashi, Yuki Izumi, Toshihiro Ogasawara, Satoshi Okada, Naoto Sato, Chiemi Tobiume, Makoto Otsuka, Kenji Miyamoto, Licht Tsuchiya, Koichiro Kawazoe, Kazuyoshi Kato, Yukinari Nishioka, Yasuhiko Cancer Sci Original Articles Podoplanin (aggrus) is highly expressed in several types of cancers, including malignant pleural mesothelioma (MPM). Previously, we developed a rat anti‐human podoplanin mAb, NZ‐1, and a rat–human chimeric anti‐human podoplanin antibody, NZ‐8, derived from NZ‐1, which induced antibody‐dependent cellular cytotoxicity (ADCC) and complement‐dependent cytotoxicity against podoplanin‐positive MPM cell lines. In this study, we showed the antitumor effect of NZ‐1, NZ‐8, and NZ‐12, a novel rat–human chimeric anti‐human podoplanin antibody derived from NZ‐1, in an MPM orthotopic xenograft SCID mouse model. Treatment with NZ‐1 and rat NK (CD161a(+)) cells inhibited the growth of tumors and the production of pleural effusion in NCI‐H290/PDPN or NCI‐H226 orthotopic xenograft mouse models. NZ‐8 and human natural killer (NK) (CD56(+)) cells also inhibited tumor growth and pleural effusion in MPM orthotopic xenograft mice. Furthermore, NZ‐12 induced potent ADCC mediated by human MNC, compared with either NZ‐1 or NZ‐8. Antitumor effects were observed following treatment with NZ‐12 and human NK (CD56(+)) cells in MPM orthotopic xenograft mice. In addition, combined immunotherapy using the ADCC activity of NZ‐12 mediated by human NK (CD56(+)) cells with pemetrexed, led to enhanced antitumor effects in MPM orthotopic xenograft mice. These results strongly suggest that combination therapy with podoplanin‐targeting immunotherapy using both NZ‐12 and pemetrexed might provide an efficacious therapeutic strategy for the treatment of MPM. John Wiley and Sons Inc. 2016-08-25 2016-09 /pmc/articles/PMC5021042/ /pubmed/27294401 http://dx.doi.org/10.1111/cas.12985 Text en © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Abe, Shinji Kaneko, Mika Kato Tsuchihashi, Yuki Izumi, Toshihiro Ogasawara, Satoshi Okada, Naoto Sato, Chiemi Tobiume, Makoto Otsuka, Kenji Miyamoto, Licht Tsuchiya, Koichiro Kawazoe, Kazuyoshi Kato, Yukinari Nishioka, Yasuhiko Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
title | Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
title_full | Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
title_fullStr | Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
title_full_unstemmed | Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
title_short | Antitumor effect of novel anti‐podoplanin antibody NZ‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
title_sort | antitumor effect of novel anti‐podoplanin antibody nz‐12 against malignant pleural mesothelioma in an orthotopic xenograft model |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5021042/ https://www.ncbi.nlm.nih.gov/pubmed/27294401 http://dx.doi.org/10.1111/cas.12985 |
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