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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
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.
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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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