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Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer
Ovarian cancer has a high recurrence rate after platinum‐based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer‐specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV‐3, and generated hybridoma clones. Several rounds of screening y...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541015/ https://www.ncbi.nlm.nih.gov/pubmed/32648337 http://dx.doi.org/10.1111/cas.14566 |
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author | Ke, Feng‐Yi Chen, Wan‐Yu Lin, Ming‐Chieh Hwang, Yu‐Chyi Kuo, Kuan‐Ting Wu, Han‐Chung |
author_facet | Ke, Feng‐Yi Chen, Wan‐Yu Lin, Ming‐Chieh Hwang, Yu‐Chyi Kuo, Kuan‐Ting Wu, Han‐Chung |
author_sort | Ke, Feng‐Yi |
collection | PubMed |
description | Ovarian cancer has a high recurrence rate after platinum‐based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer‐specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV‐3, and generated hybridoma clones. Several rounds of screening yielded 30 monoclonal antibodies (mAbs) with no cross‐reactivity to normal cells. Among these mAbs, OV‐Ab 30‐7 was found to target integrin α3 and upregulate p53 and p21, while stimulating the apoptosis of cancer cells. We further found that binding of integrin α3 by OV‐Ab 30‐7 impaired laminin‐induced focal adhesion kinase phosphorylation. The mAb alone or in combination with carboplatin and paclitaxel inhibited tumor progression and prolonged survival of tumor‐bearing mice. Moreover, immunohistochemical staining of ovarian patient specimens revealed higher levels of integrin α3 in cancer cells compared with normal cells. By querying online clinical databases, we found that elevated ITGA3 expression in ovarian cancer is associated with poor prognosis. Taken together, our data suggest that the novel mAb, OV‐Ab 30‐7, may be considered as a potential therapeutic for ovarian cancer. |
format | Online Article Text |
id | pubmed-7541015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-75410152020-10-09 Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer Ke, Feng‐Yi Chen, Wan‐Yu Lin, Ming‐Chieh Hwang, Yu‐Chyi Kuo, Kuan‐Ting Wu, Han‐Chung Cancer Sci Basic and Clinical Immunology Ovarian cancer has a high recurrence rate after platinum‐based chemotherapy. To improve the treatment of ovarian cancer and identify ovarian cancer‐specific antibodies, we immunized mice with the human ovarian carcinoma cell line, SKOV‐3, and generated hybridoma clones. Several rounds of screening yielded 30 monoclonal antibodies (mAbs) with no cross‐reactivity to normal cells. Among these mAbs, OV‐Ab 30‐7 was found to target integrin α3 and upregulate p53 and p21, while stimulating the apoptosis of cancer cells. We further found that binding of integrin α3 by OV‐Ab 30‐7 impaired laminin‐induced focal adhesion kinase phosphorylation. The mAb alone or in combination with carboplatin and paclitaxel inhibited tumor progression and prolonged survival of tumor‐bearing mice. Moreover, immunohistochemical staining of ovarian patient specimens revealed higher levels of integrin α3 in cancer cells compared with normal cells. By querying online clinical databases, we found that elevated ITGA3 expression in ovarian cancer is associated with poor prognosis. Taken together, our data suggest that the novel mAb, OV‐Ab 30‐7, may be considered as a potential therapeutic for ovarian cancer. John Wiley and Sons Inc. 2020-08-07 2020-10 /pmc/articles/PMC7541015/ /pubmed/32648337 http://dx.doi.org/10.1111/cas.14566 Text en © 2020 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 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 | Basic and Clinical Immunology Ke, Feng‐Yi Chen, Wan‐Yu Lin, Ming‐Chieh Hwang, Yu‐Chyi Kuo, Kuan‐Ting Wu, Han‐Chung Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
title | Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
title_full | Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
title_fullStr | Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
title_full_unstemmed | Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
title_short | Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
title_sort | novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer |
topic | Basic and Clinical Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541015/ https://www.ncbi.nlm.nih.gov/pubmed/32648337 http://dx.doi.org/10.1111/cas.14566 |
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