1. Novel monoclonal antibody against integrin α3 shows therapeutic potential for ovarian cancer
- Author
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Kuan-Ting Kuo, Feng-Yi Ke, Yu-Chyi Hwang, Han-Chung Wu, Wan-Yu Chen, and Ming-Chieh Lin
- Subjects
0301 basic medicine ,Cancer Research ,endocrine system diseases ,Integrin alpha3 ,Apoptosis ,Carboplatin ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Basic and Clinical Immunology ,Ovarian carcinoma ,Tumor Cells, Cultured ,Ovarian Neoplasms ,Mice, Inbred BALB C ,biology ,Antibodies, Monoclonal ,General Medicine ,Prognosis ,female genital diseases and pregnancy complications ,ovarian cancer ,Oncology ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Original Article ,Female ,Antibody ,Cyclin-Dependent Kinase Inhibitor p21 ,Paclitaxel ,medicine.drug_class ,Monoclonal antibody ,Cell Line ,03 medical and health sciences ,laminin ,medicine ,Human Umbilical Vein Endothelial Cells ,Animals ,Humans ,cell apoptosis ,integrin α3 ,business.industry ,focal adhesion kinase ,Carcinoma ,medicine.disease ,HCT116 Cells ,Disease Models, Animal ,030104 developmental biology ,chemistry ,Tumor progression ,monoclonal antibody ,Cancer cell ,biology.protein ,Cancer research ,Neoplasm Recurrence, Local ,Tumor Suppressor Protein p53 ,Ovarian cancer ,business - Abstract
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., The novel mAb, OV‐Ab 30‐7, can induce ovarian cancer cell apoptosis, and blockage integrin‐laminin signaling, and may be considered as a potential therapeutic for ovarian cancer.
- Published
- 2020