Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ke, Feng‐Yi, Chen, Wan‐Yu, Lin, Ming‐Chieh, Hwang, Yu‐Chyi, Kuo, Kuan‐Ting, Wu, Han‐Chung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
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
_version_ 1783591319119069184
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
work_keys_str_mv AT kefengyi novelmonoclonalantibodyagainstintegrina3showstherapeuticpotentialforovariancancer
AT chenwanyu novelmonoclonalantibodyagainstintegrina3showstherapeuticpotentialforovariancancer
AT linmingchieh novelmonoclonalantibodyagainstintegrina3showstherapeuticpotentialforovariancancer
AT hwangyuchyi novelmonoclonalantibodyagainstintegrina3showstherapeuticpotentialforovariancancer
AT kuokuanting novelmonoclonalantibodyagainstintegrina3showstherapeuticpotentialforovariancancer
AT wuhanchung novelmonoclonalantibodyagainstintegrina3showstherapeuticpotentialforovariancancer